Skip to main content

Advertisement

SpringerLink
Log in

Neutrophil-Induced Liver Injury and Interactions Between Neutrophils and Liver Sinusoidal Endothelial Cells

  • Review
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Neutrophils are the most abundant type of leukocytes with diverse functions in immune defense including production of reactive oxygen species, bacteriocidal proteins, neutrophil extracellular traps, and pro-inflammatory mediators. However, aberrant accumulation of neutrophils in host tissues and excessive release of bacteriocidal compounds can lead to unexpected injury to host organs. Neutrophil-mediated liver injury has been reported in various types of liver diseases including liver ischemia/reperfusion injury, nonalcoholic fatty liver disease, endotoxin-induced liver injury, alcoholic liver disease, and drug-induced liver injury. Yet the mechanisms of neutrophil-induced hepatotoxicity in different liver diseases are complicated. Current knowledge of these mechanisms are summarized in this review. In addition, a substantial body of evidence has emerged showing that liver sinusoidal endothelial cells (LSECs) participate in several key steps of neutrophil-mediated liver injury including neutrophil recruitment, adhesion, transmigration, and activation. This review also highlights the current understanding of the interactions between LSECs and neutrophils in liver injury. The future challenge is to explore new targets for selectively interfering neutrophil-induced liver injury without impairing host defense function against microbial infection. Further understanding the role of LSECs in neutrophil-induced hepatotoxicity would aid in developing more selective therapeutic approaches for liver disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data Availability

Not applicable.

Code Availability

Not applicable.

References

  1. Doring, Y., O. Soehnlein, and C. Weber. 2017. Neutrophil extracellular traps in atherosclerosis and atherothrombosis. Circulation Research 120 (4): 736–743.

    Article  PubMed  CAS  Google Scholar 

  2. Liew, P.X., and P. Kubes. 2019. The neutrophil’s role during health and disease. Physiological Reviews 99 (2): 1223–1248.

    Article  CAS  PubMed  Google Scholar 

  3. Amulic, B., C. Cazalet, G.L. Hayes, K.D. Metzler, and A. Zychlinsky. 2012. Neutrophil function: from mechanisms to disease. Annual Review of Immunology 30: 459–489.

    Article  CAS  PubMed  Google Scholar 

  4. McDonald, B., C.N. Jenne, L. Zhuo, K. Kimata, and P. Kubes. 2013. Kupffer cells and activation of endothelial TLR4 coordinate neutrophil adhesion within liver sinusoids during endotoxemia. American Journal of Physiology. Gastrointestinal and Liver Physiology 305 (11): G797–G806.

    Article  CAS  PubMed  Google Scholar 

  5. Yazdani, H.O., H.W. Chen, S. Tohme, S. Tai, D.J. van der Windt, P. Loughran, B.R. Rosborough, et al. 2017. IL-33 exacerbates liver sterile inflammation by amplifying neutrophil extracellular trap formation. Journal of Hepatology.

  6. Sakurai, K., T. Miyashita, M. Okazaki, T. Yamaguchi, Y. Ohbatake, S. Nakanuma, K. Okamoto, et al. 2017. Role for neutrophil extracellular traps (NETs) and platelet aggregation in early sepsis-induced hepatic dysfunction. Vivo 31 (6): 1051–1058.

    CAS  Google Scholar 

  7. Papayannopoulos, V. 2018. Neutrophil extracellular traps in immunity and disease. Nature Reviews. Immunology 18 (2): 134–147.

    Article  CAS  PubMed  Google Scholar 

  8. Honda, M., T. Takeichi, S. Hashimoto, D. Yoshii, K. Isono, S. Hayashida, Y. Ohya, H. Yamamoto, Y. Sugawara, and Y. Inomata. 2017. Intravital imaging of neutrophil recruitment reveals the efficacy of FPR1 blockade in hepatic ischemia-reperfusion injury. Journal of Immunology 198 (4): 1718–1728.

    Article  CAS  Google Scholar 

  9. Eltzschig, H.K., and T. Eckle. 2011. Ischemia and reperfusion--from mechanism to translation. Nature Medicine 17 (11): 1391–1401.

    Article  CAS  PubMed  Google Scholar 

  10. Zhai, Y., H. Petrowsky, J.C. Hong, R.W. Busuttil, and J.W. Kupiec-Weglinski. 2013. Ischaemia-reperfusion injury in liver transplantation--from bench to bedside. Nature Reviews. Gastroenterology & Hepatology 10 (2): 79–89.

    Article  CAS  Google Scholar 

  11. Martinez-Mier, G., L.H. Toledo-Pereyra, J.E. McDuffie, R.L. Warner, and P.A. Ward. 2001. Neutrophil depletion and chemokine response after liver ischemia and reperfusion. Journal of Investigative Surgery 14 (2): 99–107.

    Article  CAS  PubMed  Google Scholar 

  12. Chen, Y.X., M. Sato, K. Kawachi, and Y. Abe. 2006. Neutrophil-mediated liver injury during hepatic ischemia-reperfusion in rats. Hepatobiliary & Pancreatic Diseases International 5 (3): 436–442.

    CAS  Google Scholar 

  13. Kono, H., H. Fujii, M. Ogiku, N. Hosomura, H. Amemiya, M. Tsuchiya, and M. Hara. 2011. Role of IL-17A in neutrophil recruitment and hepatic injury after warm ischemia-reperfusion mice. Journal of Immunology 187 (9): 4818–4825.

    Article  CAS  Google Scholar 

  14. Li, S., X. Zheng, H. Li, J. Zheng, X. Chen, W. Liu, Y. Tai, Y. Zhang, G. Wang, and Y. Yang. 2018. Mesenchymal stem cells ameliorate hepatic ischemia/reperfusion injury via inhibition of neutrophil recruitment. Journal of Immunology Research 2018: 7283703.

    PubMed  PubMed Central  Google Scholar 

  15. Kataoka, M., H. Shimizu, N. Mitsuhashi, M. Ohtsuka, Y. Wakabayashi, H. Ito, F. Kimura, K. Nakagawa, H. Yoshidome, Y. Shimizu, and M. Miyazaki. 2002. Effect of cold-ischemia time on C-X-C chemokine expression and neutrophil accumulation in the graft liver after orthotopic liver transplantation in rats. Transplantation 73 (11): 1730–1735.

    Article  CAS  PubMed  Google Scholar 

  16. Yamaguchi, Y., K. Okabe, J. Liang, H. Ohshiro, K. Ishihara, S. Uchino, J.L. Zhang, H. Hidaka, S. Yamada, and M. Ogawa. 2000. Thrombin and factor Xa enhance neutrophil chemoattractant production after ischemia/reperfusion in the rat liver. The Journal of Surgical Research 92 (1): 96–102.

    Article  CAS  PubMed  Google Scholar 

  17. Urisono, Y., A. Sakata, H. Matsui, S. Kasuda, S. Ono, K. Yoshimoto, K. Nishio, M. Sho, M. Akiyama, T. Miyata, K. Okuchi, S. Nishimura, and M. Sugimoto. 2018. Von Willebrand factor aggravates hepatic ischemia-reperfusion injury by promoting neutrophil recruitment in mice. Thrombosis and Haemostasis 118 (4): 700–708.

    Article  PubMed  Google Scholar 

  18. Serizawa, A., S. Nakamura, S. Baba Suzuki, and M. Nakano. 1996. Involvement of platelet-activating factor in cytokine production and neutrophil activation after hepatic ischemia-reperfusion. Hepatology 23 (6): 1656–1663.

    Article  CAS  PubMed  Google Scholar 

  19. Xu, P., J. Zhang, H. Wang, G. Wang, C.Y. Wang, and J. Zhang. 2017. CCR2 dependent neutrophil activation and mobilization rely on TLR4-p38 axis during liver ischemia-reperfusion injury. American Journal of Translational Research 9 (6): 2878–2890.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhang, P., K. Yue, X. Liu, X. Yan, Z. Yang, J. Duan, C. Xia, X. Xu, M. Zhang, L. Liang, L. Wang, and H. Han. 2020. Endothelial Notch activation promotes neutrophil transmigration via downregulating endomucin to aggravate hepatic ischemia/reperfusion injury. Science China. Life Sciences 63 (3): 375–387.

    Article  CAS  PubMed  Google Scholar 

  21. Sun, L., Q. Wu, Y. Nie, N. Cheng, R. Wang, G. Wang, D. Zhang, H. He, R.D. Ye, and F. Qian. 2018. A role for MK2 in enhancing neutrophil-derived ros production and aggravating liver ischemia/reperfusion injury. Frontiers in Immunology 9: 2610.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Bzeizi, K.I., R. Jalan, I. MacGregor, O. Drummond, A. Lee, and P.C. Hayes. 1996. Neutrophil elastase: a determinant of endothelial damage and reperfusion injury after liver transplantation? Transplantation 62 (7): 916–920.

    Article  CAS  PubMed  Google Scholar 

  23. Otsuka, M., Y. Takada, K. Fukunaga, H. Taniguchi, and T. Todoroki. 2001. Activation of intracellular neutrophil elastase in the transplantation of ischemic liver. European Surgical Research 33 (5-6): 355–360.

    Article  CAS  PubMed  Google Scholar 

  24. Kushimoto, S., K. Okajima, M. Uchiba, K. Murakami, N. Harada, H. Okabe, and K. Takatsuki. 1996. Role of granulocyte elastase in ischemia/reperfusion injury of rat liver. Critical Care Medicine 24 (11): 1908–1912.

    Article  CAS  PubMed  Google Scholar 

  25. Huang, H., S. Tohme, A.B. Al-Khafaji, S. Tai, P. Loughran, L. Chen, S. Wang, et al. 2015. Damage-associated molecular pattern-activated neutrophil extracellular trap exacerbates sterile inflammatory liver injury. Hepatology 62 (2): 600–614.

    Article  CAS  PubMed  Google Scholar 

  26. Arumugam, S., K. Girish Subbiah, K. Kemparaju, and C. Thirunavukkarasu. 2018. Neutrophil extracellular traps in acrolein promoted hepatic ischemia reperfusion injury: therapeutic potential of NOX2 and p38MAPK inhibitors. Journal of Cellular Physiology 233 (4): 3244–3261.

    Article  CAS  PubMed  Google Scholar 

  27. Rinella, M.E. 2015. Nonalcoholic fatty liver disease: a systematic review. JAMA 313 (22): 2263–2273.

    Article  CAS  PubMed  Google Scholar 

  28. Williams, C.D., J. Stengel, M.I. Asike, D.M. Torres, J. Shaw, M. Contreras, C.L. Landt, and S.A. Harrison. 2011. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology 140 (1): 124–131.

    Article  PubMed  Google Scholar 

  29. Loomba, R., and A.J. Sanyal. 2013. The global NAFLD epidemic. Nature Reviews. Gastroenterology & Hepatology 10 (11): 686–690.

    Article  CAS  Google Scholar 

  30. Hwang, S., Y. He, X. Xiang, W. Seo, S.J. Kim, J. Ma, T. Ren, et al. 2019. Interleukin-22 ameliorates neutrophil-driven nonalcoholic steatohepatitis through multiple targets. Hepatology.

  31. Ou, R., J. Liu, M. Lv, J. Wang, J. Wang, L. Zhu, L. Zhao, and Y. Xu. 2017. Neutrophil depletion improves diet-induced non-alcoholic fatty liver disease in mice. Endocrine 57 (1): 72–82.

    Article  CAS  PubMed  Google Scholar 

  32. Zhou, Z., M.J. Xu, Y. Cai, W. Wang, J.X. Jiang, Z.V. Varga, D. Feng, P. Pacher, G. Kunos, N.J. Torok, and B. Gao. 2018. Neutrophil-hepatic stellate cell interactions promote fibrosis in experimental steatohepatitis. Cellular and Molecular Gastroenterology and Hepatology 5 (3): 399–413.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Zang, S., L. Wang, X. Ma, G. Zhu, Z. Zhuang, Y. Xun, F. Zhao, W. Yang, J. Liu, Y. Luo, Y. Liu, D. Ye, and J. Shi. 2015. Neutrophils play a crucial role in the early stage of nonalcoholic steatohepatitis via neutrophil elastase in mice. Cell Biochemistry and Biophysics 73 (2): 479–487.

    Article  CAS  PubMed  Google Scholar 

  34. Rensen, S.S., V. Bieghs, S. Xanthoulea, E. Arfianti, J.A. Bakker, R. Shiri-Sverdlov, M.H. Hofker, J.W. Greve, and W.A. Buurman. 2012. Neutrophil-derived myeloperoxidase aggravates non-alcoholic steatohepatitis in low-density lipoprotein receptor-deficient mice. PLoS One 7 (12): e52411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. van der Windt, D.J., V. Sud, H. Zhang, P.R. Varley, J. Goswami, H.O. Yazdani, S. Tohme, P. Loughran, R.M. O'Doherty, M.I. Minervini, H. Huang, R.L. Simmons, and A. Tsung. 2018. Neutrophil extracellular traps promote inflammation and development of hepatocellular carcinoma in nonalcoholic steatohepatitis. Hepatology 68 (4): 1347–1360.

    Article  PubMed  CAS  Google Scholar 

  36. Zou, W., R.A. Roth, H.S. Younis, E. Malle, and P.E. Ganey. 2011. Neutrophil-cytokine interactions in a rat model of sulindac-induced idiosyncratic liver injury. Toxicology 290 (2-3): 278–285.

    Article  PubMed  CAS  Google Scholar 

  37. Hewett, J.A., A.E. Schultze, S. VanCise, and R.A. Roth. 1992. Neutrophil depletion protects against liver injury from bacterial endotoxin. Laboratory Investigation 66 (3): 347–361.

    CAS  PubMed  Google Scholar 

  38. Zhao, X., X. Shi, Z. Zhang, H. Ma, X. Yuan, and Y. Ding. 2016. Combined treatment with MSC transplantation and neutrophil depletion ameliorates D-GalN/LPS-induced acute liver failure in rats. Clinics and Research in Hepatology and Gastroenterology 40 (6): 730–738.

    Article  CAS  PubMed  Google Scholar 

  39. Deutschman, C.S., B.A. Haber, K. Andrejko, D.E. Cressman, R. Harrison, E. Elenko, and R. Taub. 1996. Increased expression of cytokine-induced neutrophil chemoattractant in septic rat liver. The American Journal of Physiology 271 (3 Pt 2): R593–R600.

    CAS  PubMed  Google Scholar 

  40. Deng, X., J.P. Luyendyk, W. Zou, J. Lu, E. Malle, P.E. Ganey, and R.A. Roth. 2007. Neutrophil interaction with the hemostatic system contributes to liver injury in rats cotreated with lipopolysaccharide and ranitidine. The Journal of Pharmacology and Experimental Therapeutics 322 (2): 852–861.

    Article  CAS  PubMed  Google Scholar 

  41. Chosay, J.G., N.A. Essani, C.J. Dunn, and H. Jaeschke. 1997. Neutrophil margination and extravasation in sinusoids and venules of liver during endotoxin-induced injury. The American Journal of Physiology 272 (5 Pt 1): G1195–G1200.

    CAS  PubMed  Google Scholar 

  42. Kwon, A.H., and Z. Qiu. 2007. Neutrophil elastase inhibitor prevents endotoxin-induced liver injury following experimental partial hepatectomy. The British Journal of Surgery 94 (5): 609–619.

    Article  CAS  PubMed  Google Scholar 

  43. Luyendyk, J.P., P.J. Shaw, C.D. Green, J.F. Maddox, P.E. Ganey, and R.A. Roth. 2005. Coagulation-mediated hypoxia and neutrophil-dependent hepatic injury in rats given lipopolysaccharide and ranitidine. The Journal of Pharmacology and Experimental Therapeutics 314 (3): 1023–1031.

    Article  CAS  PubMed  Google Scholar 

  44. Taieb, J., P. Mathurin, C. Elbim, P. Cluzel, M. Arce-Vicioso, B. Bernard, P. Opolon, M.A. Gougerot-Pocidalo, T. Poynard, and S. Chollet-Martin. 2000. Blood neutrophil functions and cytokine release in severe alcoholic hepatitis: effect of corticosteroids. Journal of Hepatology 32 (4): 579–586.

    Article  CAS  PubMed  Google Scholar 

  45. Takahashi, T., T. Kamimura, and F. Ichida. 1987. Ultrastructural findings on polymorphonuclear leucocyte infiltration and acute hepatocellular damage in alcoholic hepatitis. Liver 7 (6): 347–358.

    Article  CAS  PubMed  Google Scholar 

  46. Potts, J.R., N. Farahi, M.R. Howard, M.R. Taylor, S. Heard, A.N. Shankar, G.J. Alexander, E.R. Chilvers, S. Verma, and A.M. Peters. 2018. In vivo imaging of hepatic neutrophil migration in severe alcoholic hepatitis with (111)In-radiolabelled leucocytes. Bioscience Reports 38 (4).

  47. Roh, Y.S., B. Zhang, R. Loomba, and E. Seki. 2015. TLR2 and TLR9 contribute to alcohol-mediated liver injury through induction of CXCL1 and neutrophil infiltration. American Journal of Physiology. Gastrointestinal and Liver Physiology 309 (1): G30–G41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Degre, D., A. Lemmers, T. Gustot, R. Ouziel, E. Trepo, P. Demetter, L. Verset, et al. 2012. Hepatic expression of CCL2 in alcoholic liver disease is associated with disease severity and neutrophil infiltrates. Clinical and Experimental Immunology 169 (3): 302–310.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Sheron, N., G. Bird, J. Koskinas, B. Portmann, M. Ceska, I. Lindley, and R. Williams. 1993. Circulating and tissue levels of the neutrophil chemotaxin interleukin-8 are elevated in severe acute alcoholic hepatitis, and tissue levels correlate with neutrophil infiltration. Hepatology 18 (1): 41–46.

    CAS  PubMed  Google Scholar 

  50. Apte, U.M., A. Banerjee, R. McRee, E. Wellberg, and S.K. Ramaiah. 2005. Role of osteopontin in hepatic neutrophil infiltration during alcoholic steatohepatitis. Toxicology and Applied Pharmacology 207 (1): 25–38.

    Article  CAS  PubMed  Google Scholar 

  51. Banerjee, A., U.M. Apte, R. Smith, and S.K. Ramaiah. 2006. Higher neutrophil infiltration mediated by osteopontin is a likely contributing factor to the increased susceptibility of females to alcoholic liver disease. The Journal of Pathology 208 (4): 473–485.

    Article  CAS  PubMed  Google Scholar 

  52. Zhang, Z., G. Xie, L. Liang, H. Liu, J. Pan, H. Cheng, H. Wang, A. Qu, and Y. Wang. 2018. RIPK3-mediated necroptosis and neutrophil infiltration are associated with poor prognosis in patients with alcoholic cirrhosis. Journal of Immunology Research 2018: 1509851.

    PubMed  PubMed Central  Google Scholar 

  53. Stanley, A.J., I.R. MacGregor, J.F. Dillon, I.A. Bouchier, and P.C. Hayes. 1996. Neutrophil activation in chronic liver disease. European Journal of Gastroenterology & Hepatology 8 (2): 135–138.

    Article  CAS  Google Scholar 

  54. Czepielewski, R.S., N. Jaeger, P.E. Marques, M.M. Antunes, M.M. Rigo, D.M. Alvarenga, R.V. Pereira, R.D. da Silva, T.G. Lopes, V.D. da Silva, B.N. Porto, G.B. Menezes, and C. Bonorino. 2017. GRPR antagonist protects from drug-induced liver injury by impairing neutrophil chemotaxis and motility. European Journal of Immunology 47 (4): 646–657.

    Article  CAS  PubMed  Google Scholar 

  55. Moles, A., L. Murphy, C.L. Wilson, J.B. Chakraborty, C. Fox, E.J. Park, J. Mann, F. Oakley, R. Howarth, J. Brain, S. Masson, M. Karin, E. Seki, and D.A. Mann. 2014. A TLR2/S100A9/CXCL-2 signaling network is necessary for neutrophil recruitment in acute and chronic liver injury in the mouse. Journal of Hepatology 60 (4): 782–791.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Marques, P.E., S.S. Amaral, D.A. Pires, L.L. Nogueira, F.M. Soriani, B.H. Lima, G.A. Lopes, et al. 2012. Chemokines and mitochondrial products activate neutrophils to amplify organ injury during mouse acute liver failure. Hepatology 56 (5): 1971–1982.

    Article  CAS  PubMed  Google Scholar 

  57. Williams, C.D., M.L. Bajt, A. Farhood, and H. Jaeschke. 2010. Acetaminophen-induced hepatic neutrophil accumulation and inflammatory liver injury in CD18-deficient mice. Liver International 30 (9): 1280–1292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Liu, Z.X., D. Han, B. Gunawan, and N. Kaplowitz. 2006. Neutrophil depletion protects against murine acetaminophen hepatotoxicity. Hepatology 43 (6): 1220–1230.

    Article  CAS  PubMed  Google Scholar 

  59. Zhou, X., L. Yang, X. Fan, X. Zhao, N. Chang, L. Yang, and L. Li. 2020. Neutrophil chemotaxis and NETosis in murine chronic liver injury via cannabinoid receptor 1/ Galphai/o/ ROS/ p38 MAPK signaling pathway. Cells 9 (2).

  60. Mittal, S., H.B. El-Serag, Y.H. Sada, F. Kanwal, Z. Duan, S. Temple, S.B. May, J.R. Kramer, P.A. Richardson, and J.A. Davila. 2016. Hepatocellular carcinoma in the absence of cirrhosis in United States Veterans is associated with nonalcoholic fatty liver disease. Clinical Gastroenterology and Hepatology 14 (1): 124–131 e121.

    Article  CAS  PubMed  Google Scholar 

  61. Shelat, V.G. 2020. Role of inflammatory indices in management of hepatocellular carcinoma-neutrophil to lymphocyte ratio. Ann Transl Med 8 (15): 912.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Zhou, S.L., Z. Dai, Z.J. Zhou, X.Y. Wang, G.H. Yang, Z. Wang, X.W. Huang, J. Fan, and J. Zhou. 2012. Overexpression of CXCL5 mediates neutrophil infiltration and indicates poor prognosis for hepatocellular carcinoma. Hepatology 56 (6): 2242–2254.

    Article  CAS  PubMed  Google Scholar 

  63. Li, L., L. Xu, J. Yan, Z.J. Zhen, Y. Ji, C.Q. Liu, W.Y. Lau, L. Zheng, and J. Xu. 2015. CXCR2-CXCL1 axis is correlated with neutrophil infiltration and predicts a poor prognosis in hepatocellular carcinoma. Journal of Experimental & Clinical Cancer Research 34: 129.

    Article  CAS  Google Scholar 

  64. Kuang, D.M., Q. Zhao, Y. Wu, C. Peng, J. Wang, Z. Xu, X.Y. Yin, and L. Zheng. 2011. Peritumoral neutrophils link inflammatory response to disease progression by fostering angiogenesis in hepatocellular carcinoma. Journal of Hepatology 54 (5): 948–955.

    Article  CAS  PubMed  Google Scholar 

  65. Wislez, M., N. Rabbe, J. Marchal, B. Milleron, B. Crestani, C. Mayaud, M. Antoine, P. Soler, and J. Cadranel. 2003. Hepatocyte growth factor production by neutrophils infiltrating bronchioloalveolar subtype pulmonary adenocarcinoma: role in tumor progression and death. Cancer Research 63 (6): 1405–1412.

    CAS  PubMed  Google Scholar 

  66. Queen, M.M., R.E. Ryan, R.G. Holzer, C.R. Keller-Peck, and C.L. Jorcyk. 2005. Breast cancer cells stimulate neutrophils to produce oncostatin M: potential implications for tumor progression. Cancer Research 65 (19): 8896–8904.

    Article  CAS  PubMed  Google Scholar 

  67. Houghton, A.M., D.M. Rzymkiewicz, H. Ji, A.D. Gregory, E.E. Egea, H.E. Metz, D.B. Stolz, S.R. Land, L.A. Marconcini, C.R. Kliment, K.M. Jenkins, K.A. Beaulieu, M. Mouded, S.J. Frank, K.K. Wong, and S.D. Shapiro. 2010. Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor growth. Nature Medicine 16 (2): 219–223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wilson, C.L., D. Jurk, N. Fullard, P. Banks, A. Page, S. Luli, A.M. Elsharkawy, R.G. Gieling, J.B. Chakraborty, C. Fox, C. Richardson, K. Callaghan, G.E. Blair, N. Fox, A. Lagnado, J.F. Passos, A.J. Moore, G.R. Smith, D.G. Tiniakos, J. Mann, F. Oakley, and D.A. Mann. 2015. NFkappaB1 is a suppressor of neutrophil-driven hepatocellular carcinoma. Nature Communications 6: 6818.

    Article  CAS  PubMed  Google Scholar 

  69. Seo, J.D., J.Y. Gu, H.S. Jung, Y.J. Kim, and H.K. Kim. 2019. Contact system activation and neutrophil extracellular trap markers: risk factors for portal vein thrombosis in patients with hepatocellular carcinoma. Clinical and Applied Thrombosis/Hemostasis 25: 1076029618825310.

    Article  CAS  PubMed Central  Google Scholar 

  70. Yang, L.Y., Q. Luo, L. Lu, W.W. Zhu, H.T. Sun, R. Wei, Z.F. Lin, X.Y. Wang, C.Q. Wang, M. Lu, H.L. Jia, J.H. Chen, J.B. Zhang, and L.X. Qin. 2020. Increased neutrophil extracellular traps promote metastasis potential of hepatocellular carcinoma via provoking tumorous inflammatory response. Journal of Hematology & Oncology 13 (1): 3.

    Article  CAS  Google Scholar 

  71. Khanam, A., N. Trehanpati, P. Riese, A. Rastogi, C.A. Guzman, and S.K. Sarin. 2017. Blockade of neutrophil’s chemokine receptors CXCR1/2 abrogate liver damage in acute-on-chronic liver failure. Frontiers in Immunology 8: 464.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Tang, Y., H. Li, J. Li, Y. Liu, Y. Li, J. Zhou, J. Zhou, X. Lu, W. Zhao, J. Hou, X.Y. Wang, Z. Chen, and D. Zuo. 2018. Macrophage scavenger receptor 1 contributes to pathogenesis of fulminant hepatitis via neutrophil-mediated complement activation. Journal of Hepatology 68 (4): 733–743.

    Article  CAS  PubMed  Google Scholar 

  73. Takai, S., K. Kimura, M. Nagaki, S. Satake, K. Kakimi, and H. Moriwaki. 2005. Blockade of neutrophil elastase attenuates severe liver injury in hepatitis B transgenic mice. Journal of Virology 79 (24): 15142–15150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Bonder, C.S., M.N. Ajuebor, L.D. Zbytnuik, P. Kubes, and M.G. Swain. 2004. Essential role for neutrophil recruitment to the liver in concanavalin A-induced hepatitis. Journal of Immunology 172 (1): 45–53.

    Article  CAS  Google Scholar 

  75. Thannickal, V.J., and B.L. Fanburg. 2000. Reactive oxygen species in cell signaling. American Journal of Physiology. Lung Cellular and Molecular Physiology 279 (6): L1005–L1028.

    Article  CAS  PubMed  Google Scholar 

  76. Green, D.R., and G. Kroemer. 2004. The pathophysiology of mitochondrial cell death. Science 305 (5684): 626–629.

    Article  CAS  PubMed  Google Scholar 

  77. Zhang, A.Y., F. Yi, S. Jin, M. Xia, Q.Z. Chen, E. Gulbins, and P.L. Li. 2007. Acid sphingomyelinase and its redox amplification in formation of lipid raft redox signaling platforms in endothelial cells. Antioxidants & Redox Signaling 9 (7): 817–828.

    Article  CAS  Google Scholar 

  78. Zhang, A.Y., F. Yi, G. Zhang, E. Gulbins, and P.L. Li. 2006. Lipid raft clustering and redox signaling platform formation in coronary arterial endothelial cells. Hypertension 47 (1): 74–80.

    Article  CAS  PubMed  Google Scholar 

  79. Jaeschke, H., A.P. Bautista, Z. Spolarics, and J.J. Spitzer. 1992. Superoxide generation by neutrophils and Kupffer cells during in vivo reperfusion after hepatic ischemia in rats. Journal of Leukocyte Biology 52 (4): 377–382.

    Article  CAS  PubMed  Google Scholar 

  80. Jaeschke, H., Y.S. Ho, M.A. Fisher, J.A. Lawson, and A. Farhood. 1999. Glutathione peroxidase-deficient mice are more susceptible to neutrophil-mediated hepatic parenchymal cell injury during endotoxemia: importance of an intracellular oxidant stress. Hepatology 29 (2): 443–450.

    Article  CAS  PubMed  Google Scholar 

  81. Yao, W., X. Han, Y. Zhang, J. Guan, M. Ge, C. Chen, S. Wu, et al. 2018. Intravenous anesthetic protects hepatocyte from reactive oxygen species-induced cellular apoptosis during liver transplantation in vivo. Oxidative Medicine and Cellular Longevity 2018: 4780615.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Farbiszewski, R., M. Chwiecko, A. Holownia, and D. Pawlowska. 1991. The decrease of superoxide dismutase activity and depletion of sulfhydryl compounds in ethanol-induced liver injury. Drug and Alcohol Dependence 28 (3): 291–294.

    Article  CAS  PubMed  Google Scholar 

  83. Conde de la Rosa, L., M.H. Schoemaker, T.E. Vrenken, M. Buist-Homan, R. Havinga, P.L. Jansen, and H. Moshage. 2006. Superoxide anions and hydrogen peroxide induce hepatocyte death by different mechanisms: involvement of JNK and ERK MAP kinases. Journal of Hepatology 44 (5): 918–929.

    Article  CAS  PubMed  Google Scholar 

  84. Ding, X., M.Y. Wang, Y.X. Yao, G.Y. Li, and B.C. Cai. 2010. Protective effect of 5-hydroxymethylfurfural derived from processed Fructus Corni on human hepatocyte LO2 injured by hydrogen peroxide and its mechanism. Journal of Ethnopharmacology 128 (2): 373–376.

    Article  CAS  PubMed  Google Scholar 

  85. Jones, B.E., C.R. Lo, H. Liu, Z. Pradhan, L. Garcia, A. Srinivasan, K.L. Valentino, and M.J. Czaja. 2000. Role of caspases and NF-kappaB signaling in hydrogen peroxide- and superoxide-induced hepatocyte apoptosis. American Journal of Physiology. Gastrointestinal and Liver Physiology 278 (5): G693–G699.

    Article  CAS  PubMed  Google Scholar 

  86. Casini, A., E. Ceni, R. Salzano, P. Biondi, M. Parola, A. Galli, M. Foschi, A. Caligiuri, M. Pinzani, and C. Surrenti. 1997. Neutrophil-derived superoxide anion induces lipid peroxidation and stimulates collagen synthesis in human hepatic stellate cells: role of nitric oxide. Hepatology 25 (2): 361–367.

    Article  CAS  PubMed  Google Scholar 

  87. Jia, R., J. Du, L. Cao, Y. Li, O. Johnson, Z. Gu, G. Jeney, P. Xu, and G. Yin. 2019. Antioxidative, inflammatory and immune responses in hydrogen peroxide-induced liver injury of tilapia (GIFT, Oreochromis niloticus). Fish & Shellfish Immunology 84: 894–905.

    Article  CAS  Google Scholar 

  88. Sakuma, S., M. Negoro, T. Kitamura, and Y. Fujimoto. 2010. Xanthine oxidase-derived reactive oxygen species mediate 4-oxo-2-nonenal-induced hepatocyte cell death. Toxicology and Applied Pharmacology 249 (2): 127–131.

    Article  CAS  PubMed  Google Scholar 

  89. Kohli, R., X. Pan, P. Malladi, M.S. Wainwright, and P.F. Whitington. 2007. Mitochondrial reactive oxygen species signal hepatocyte steatosis by regulating the phosphatidylinositol 3-kinase cell survival pathway. The Journal of Biological Chemistry 282 (29): 21327–21336.

    Article  CAS  PubMed  Google Scholar 

  90. Brinkmann, V., and A. Zychlinsky. 2012. Neutrophil extracellular traps: is immunity the second function of chromatin? The Journal of Cell Biology 198 (5): 773–783.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Kaplan, M.J., and M. Radic. 2012. Neutrophil extracellular traps: double-edged swords of innate immunity. Journal of Immunology 189 (6): 2689–2695.

    Article  CAS  Google Scholar 

  92. Hilscher, M.B., T. Sehrawat, J.P. Arab, Z. Zeng, J. Gao, M. Liu, E. Kostallari, Y. Gao, D.A. Simonetto, U. Yaqoob, S. Cao, A. Revzin, A. Beyder, R.A. Wang, P.S. Kamath, P. Kubes, and V.H. Shah. 2019. Mechanical stretch increases expression of cxcl1 in liver sinusoidal endothelial cells to recruit neutrophils, generate sinusoidal microthombi, and promote portal hypertension. Gastroenterology 157 (1): 193–209 e199.

    Article  CAS  PubMed  Google Scholar 

  93. Kolaczkowska, E., C.N. Jenne, B.G. Surewaard, A. Thanabalasuriar, W.Y. Lee, M.J. Sanz, K. Mowen, G. Opdenakker, and P. Kubes. 2015. Molecular mechanisms of NET formation and degradation revealed by intravital imaging in the liver vasculature. Nature Communications 6: 6673.

    Article  CAS  PubMed  Google Scholar 

  94. Xu, J., X. Zhang, R. Pelayo, M. Monestier, C.T. Ammollo, F. Semeraro, F.B. Taylor, N.L. Esmon, F. Lupu, and C.T. Esmon. 2009. Extracellular histones are major mediators of death in sepsis. Nature Medicine 15 (11): 1318–1321.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Saffarzadeh, M., C. Juenemann, M.A. Queisser, G. Lochnit, G. Barreto, S.P. Galuska, J. Lohmeyer, and K.T. Preissner. 2012. Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones. PLoS One 7 (2): e32366.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Faurschou, M., and N. Borregaard. 2003. Neutrophil granules and secretory vesicles in inflammation. Microbes and Infection 5 (14): 1317–1327.

    Article  CAS  PubMed  Google Scholar 

  97. Kawai, M., N. Harada, H. Takeyama, and K. Okajima. 2010. Neutrophil elastase contributes to the development of ischemia/reperfusion-induced liver injury by decreasing the production of insulin-like growth factor-I in rats. Translational Research 155 (6): 294–304.

    Article  CAS  PubMed  Google Scholar 

  98. Jaeschke, H., and C.W. Smith. 1997. Mechanisms of neutrophil-induced parenchymal cell injury. Journal of Leukocyte Biology 61 (6): 647–653.

    Article  CAS  PubMed  Google Scholar 

  99. Nusse, O., and M. Lindau. 1988. The dynamics of exocytosis in human neutrophils. The Journal of Cell Biology 107 (6 Pt 1): 2117–2123.

    Article  CAS  PubMed  Google Scholar 

  100. Ho, J.S., J.P. Buchweitz, R.A. Roth, and P.E. Ganey. 1996. Identification of factors from rat neutrophils responsible for cytotoxicity to isolated hepatocytes. Journal of Leukocyte Biology 59 (5): 716–724.

    Article  CAS  PubMed  Google Scholar 

  101. Meyer-Hoffert, U. 2009. Neutrophil-derived serine proteases modulate innate immune responses. Front Biosci (Landmark Ed) 14: 3409–3418.

    Article  CAS  Google Scholar 

  102. Devaney, J.M., C.M. Greene, C.C. Taggart, T.P. Carroll, S.J. O'Neill, and N.G. McElvaney. 2003. Neutrophil elastase up-regulates interleukin-8 via toll-like receptor 4. FEBS Letters 544 (1-3): 129–132.

    Article  CAS  PubMed  Google Scholar 

  103. Jaeschke, H. 2003. Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning. American Journal of Physiology. Gastrointestinal and Liver Physiology 284 (1): G15–G26.

    Article  CAS  PubMed  Google Scholar 

  104. Al-Mohanna, F., S. Saleh, R.S. Parhar, and K. Collison. 2002. IL-12-dependent nuclear factor-kappaB activation leads to de novo synthesis and release of IL-8 and TNF-alpha in human neutrophils. Journal of Leukocyte Biology 72 (5): 995–1002.

    CAS  PubMed  Google Scholar 

  105. Riedemann, N.C., R.F. Guo, T.J. Hollmann, H. Gao, T.A. Neff, J.S. Reuben, C.L. Speyer, J.V. Sarma, R.A. Wetsel, F.S. Zetoune, and P.A. Ward. 2004. Regulatory role of C5a in LPS-induced IL-6 production by neutrophils during sepsis. The FASEB Journal 18 (2): 370–372.

    Article  CAS  PubMed  Google Scholar 

  106. Sugita, N., A. Kimura, Y. Matsuki, T. Yamamoto, H. Yoshie, and K. Hara. 1998. Activation of transcription factors and IL-8 expression in neutrophils stimulated with lipopolysaccharide from Porphyromonas gingivalis. Inflammation 22 (3): 253–267.

    Article  CAS  PubMed  Google Scholar 

  107. Schuster, S., B. Hurrell, and F. Tacchini-Cottier. 2013. Crosstalk between neutrophils and dendritic cells: a context-dependent process. Journal of Leukocyte Biology 94 (4): 671–675.

    Article  CAS  PubMed  Google Scholar 

  108. Costa, S., D. Bevilacqua, M.A. Cassatella, and P. Scapini. 2019. Recent advances on the crosstalk between neutrophils and B or T lymphocytes. Immunology 156 (1): 23–32.

    Article  CAS  PubMed  Google Scholar 

  109. McDonald, B., K. Pittman, G.B. Menezes, S.A. Hirota, I. Slaba, C.C. Waterhouse, P.L. Beck, D.A. Muruve, and P. Kubes. 2010. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science 330 (6002): 362–366.

    Article  CAS  PubMed  Google Scholar 

  110. Connolly, M.K., A.S. Bedrosian, A. Malhotra, J.R. Henning, J. Ibrahim, V. Vera, N.E. Cieza-Rubio, B.U. Hassan, H.L. Pachter, S. Cohen, A.B. Frey, and G. Miller. 2010. In hepatic fibrosis, liver sinusoidal endothelial cells acquire enhanced immunogenicity. Journal of Immunology 185 (4): 2200–2208.

    Article  CAS  Google Scholar 

  111. Arnould, T., R. Thibaut-Vercruyssen, N. Bouaziz, M. Dieu, J. Remacle, and C. Michiels. 2001. PGF(2alpha), a prostanoid released by endothelial cells activated by hypoxia, is a chemoattractant candidate for neutrophil recruitment. The American Journal of Pathology 159 (1): 345–357.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Kus, E., P. Kaczara, I. Czyzynska-Cichon, K. Szafranska, B. Zapotoczny, A. Kij, A. Sowinska, J. Kotlinowski, L. Mateuszuk, E. Czarnowska, M. Szymonski, and S. Chlopicki. 2019. LSEC fenestrae are preserved despite pro-inflammatory phenotype of liver sinusoidal endothelial cells in mice on high fat diet. Frontiers in Physiology 10: 6.

    Article  PubMed  PubMed Central  Google Scholar 

  113. Eksteen, B., A.J. Grant, A. Miles, S.M. Curbishley, P.F. Lalor, S.G. Hubscher, M. Briskin, M. Salmon, and D.H. Adams. 2004. Hepatic endothelial CCL25 mediates the recruitment of CCR9+ gut-homing lymphocytes to the liver in primary sclerosing cholangitis. The Journal of Experimental Medicine 200 (11): 1511–1517.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Gong, W.G., J.L. Lin, Q.X. Niu, H.M. Wang, Y.C. Zhou, S.Y. Chen, and G.W. Liang. 2015. Paeoniflorin diminishes ConA-induced IL-8 production in primary human hepatic sinusoidal endothelial cells in the involvement of ERK1/2 and Akt phosphorylation. The International Journal of Biochemistry & Cell Biology 62: 93–100.

    Article  CAS  Google Scholar 

  115. Wong, J., B. Johnston, S.S. Lee, D.C. Bullard, C.W. Smith, A.L. Beaudet, and P. Kubes. 1997. A minimal role for selectins in the recruitment of leukocytes into the inflamed liver microvasculature. The Journal of Clinical Investigation 99 (11): 2782–2790.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Khan, A.I., S.M. Kerfoot, B. Heit, L. Liu, G. Andonegui, B. Ruffell, P. Johnson, and P. Kubes. 2004. Role of CD44 and hyaluronan in neutrophil recruitment. Journal of Immunology 173 (12): 7594–7601.

    Article  CAS  Google Scholar 

  117. McDonald, B., E.F. McAvoy, F. Lam, V. Gill, C. de la Motte, R.C. Savani, and P. Kubes. 2008. Interaction of CD44 and hyaluronan is the dominant mechanism for neutrophil sequestration in inflamed liver sinusoids. The Journal of Experimental Medicine 205 (4): 915–927.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Yadav, S.S., D.N. Howell, W. Gao, D.A. Steeber, R.C. Harland, and P.A. Clavien. 1998. L-selectin and ICAM-1 mediate reperfusion injury and neutrophil adhesion in the warm ischemic mouse liver. The American Journal of Physiology 275 (6): G1341–G1352.

    CAS  PubMed  Google Scholar 

  119. Yadav, S.S., D.N. Howell, D.A. Steeber, R.C. Harland, T.F. Tedder, and P.A. Clavien. 1999. P-Selectin mediates reperfusion injury through neutrophil and platelet sequestration in the warm ischemic mouse liver. Hepatology 29 (5): 1494–1502.

    Article  CAS  PubMed  Google Scholar 

  120. Colotta, F., F. Re, N. Polentarutti, S. Sozzani, and A. Mantovani. 1992. Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products. Blood 80 (8): 2012–2020.

    Article  CAS  PubMed  Google Scholar 

  121. Honda, M., and P. Kubes. 2018. Neutrophils and neutrophil extracellular traps in the liver and gastrointestinal system. Nature Reviews. Gastroenterology & Hepatology 15 (4): 206–221.

    Article  CAS  Google Scholar 

  122. Essani, N.A., M.A. Fisher, C.A. Simmons, J.L. Hoover, A. Farhood, and H. Jaeschke. 1998. Increased P-selectin gene expression in the liver vasculature and its role in the pathophysiology of neutrophil-induced liver injury in murine endotoxin shock. Journal of Leukocyte Biology 63 (3): 288–296.

    Article  CAS  PubMed  Google Scholar 

  123. Essani, N.A., M.L. Bajt, A. Farhood, S.L. Vonderfecht, and H. Jaeschke. 1997. Transcriptional activation of vascular cell adhesion molecule-1 gene in vivo and its role in the pathophysiology of neutrophil-induced liver injury in murine endotoxin shock. Journal of Immunology 158 (12): 5941–5948.

    CAS  Google Scholar 

  124. Ito, Y., E.R. Abril, N.W. Bethea, M.K. McCuskey, C. Cover, H. Jaeschke, and R.S. McCuskey. 2006. Mechanisms and pathophysiological implications of sinusoidal endothelial cell gap formation following treatment with galactosamine/endotoxin in mice. American Journal of Physiology. Gastrointestinal and Liver Physiology 291 (2): G211–G218.

    Article  CAS  PubMed  Google Scholar 

  125. Lawson, J.A., M.A. Fisher, C.A. Simmons, A. Farhood, and H. Jaeschke. 1998. Parenchymal cell apoptosis as a signal for sinusoidal sequestration and transendothelial migration of neutrophils in murine models of endotoxin and Fas-antibody-induced liver injury. Hepatology 28 (3): 761–767.

    Article  CAS  PubMed  Google Scholar 

  126. Dharancy, S., M. Body-Malapel, A. Louvet, D. Berrebi, E. Gantier, P. Gosset, J. Viala, et al. 2010. Neutrophil migration during liver injury is under nucleotide-binding oligomerization domain 1 control. Gastroenterology 138 (4): 1546–1556 1556 e1541-1545.

    Article  CAS  PubMed  Google Scholar 

  127. Bajt, M.L., A. Farhood, and H. Jaeschke. 2001. Effects of CXC chemokines on neutrophil activation and sequestration in hepatic vasculature. American Journal of Physiology. Gastrointestinal and Liver Physiology 281 (5): G1188–G1195.

    Article  CAS  PubMed  Google Scholar 

  128. Gujral, J.S., J. Liu, A. Farhood, J.A. Hinson, and H. Jaeschke. 2004. Functional importance of ICAM-1 in the mechanism of neutrophil-induced liver injury in bile duct-ligated mice. American Journal of Physiology. Gastrointestinal and Liver Physiology 286 (3): G499–G507.

    Article  CAS  PubMed  Google Scholar 

  129. Jaeschke, H. 2000. Reactive oxygen and mechanisms of inflammatory liver injury. Journal of Gastroenterology and Hepatology 15 (7): 718–724.

    Article  CAS  PubMed  Google Scholar 

  130. Miyashita, T., S. Nakanuma, A.K. Ahmed, I. Makino, H. Hayashi, K. Oyama, H. Nakagawara, H. Tajima, H. Takamura, I. Ninomiya, S. Fushida, J.W. Harmon, and T. Ohta. 2016. Ischemia reperfusion-facilitated sinusoidal endothelial cell injury in liver transplantation and the resulting impact of extravasated platelet aggregation. European Surgery 48: 92–98.

    Article  CAS  PubMed  Google Scholar 

  131. Pasarin, M., V. La Mura, J. Gracia-Sancho, H. Garcia-Caldero, A. Rodriguez-Vilarrupla, J.C. Garcia-Pagan, J. Bosch, and J.G. Abraldes. 2012. Sinusoidal endothelial dysfunction precedes inflammation and fibrosis in a model of NAFLD. PLoS One 7 (4): e32785.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Zhuge, Y., Y. Liu, W. Xie, X. Zou, J. Xu, J. Wang, and Disease Chinese Society of Gastroenterology Committee of Hepatobiliary. 2019. Expert consensus on the clinical management of pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome. Journal of Gastroenterology and Hepatology 34 (4): 634–642.

    Article  PubMed  Google Scholar 

  133. Prince, L.R., M.K. Whyte, I. Sabroe, and L.C. Parker. 2011. The role of TLRs in neutrophil activation. Current Opinion in Pharmacology 11 (4): 397–403.

    Article  CAS  PubMed  Google Scholar 

  134. Ohtsuka, M., M. Miyazaki, Y. Kondo, and N. Nakajima. 1997. Neutrophil-mediated sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats. Hepatology 25 (3): 636–641.

    Article  CAS  PubMed  Google Scholar 

  135. Ohtsuka, M., M. Miyazaki, H. Kubosawa, Y. Kondo, H. Ito, H. Shimizu, Y. Shimizu, S. Nozawa, S. Furuya, and N. Nakajima. 2000. Role of neutrophils in sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats. Journal of Gastroenterology and Hepatology 15 (8): 880–886.

    Article  CAS  PubMed  Google Scholar 

  136. Gong, J.P., C.X. Wu, C.A. Liu, S.W. Li, Y.J. Shi, X.H. Li, and Y. Peng. 2002. Liver sinusoidal endothelial cell injury by neutrophils in rats with acute obstructive cholangitis. World Journal of Gastroenterology 8 (2): 342–345.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Shimizu, Y., M. Miyazaki, H. Ito, K. Nakagawa, S. Ambiru, H. Shimizu, and N. Nakajima. 1997. Enhanced endothelial cell injury by activated neutrophils in patients with obstructive jaundice. Journal of Hepatology 27 (5): 803–809.

    Article  CAS  PubMed  Google Scholar 

  138. Shimizu, Y., M. Miyazaki, H. Ito, K. Nakagawa, S. Ambiru, H. Shimizu, S. Nakamura, A. Okuno, S. Nozawa, Y. Nukui, H. Yoshitomi, and N. Nakajim. 1999. Enhanced polymorphonuclear neutrophil-mediated endothelial cell injury and its relation to high surgical mortality rate in cirrhotic patients. The American Journal of Gastroenterology 94 (11): 3297–3303.

    Article  CAS  PubMed  Google Scholar 

  139. Carambia, A., C. Frenzel, O.T. Bruns, D. Schwinge, R. Reimer, H. Hohenberg, S. Huber, G. Tiegs, C. Schramm, A.W. Lohse, and J. Herkel. 2013. Inhibition of inflammatory CD4 T cell activity by murine liver sinusoidal endothelial cells. Journal of Hepatology 58 (1): 112–118.

    Article  CAS  PubMed  Google Scholar 

  140. Hammoutene, A., and P.E. Rautou. 2019. Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease. Journal of Hepatology 70 (6): 1278–1291.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work is supported by the National Natural Science Foundation of China (Grant number 82070539 and 81873549).

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Peking University People’s Hospital, No.11, Xizhimen South Street, Xicheng District, Beijing, 100044, China

    Yang Wang & Yulan Liu

  2. Clinical Center of Immune-Mediated Digestive Diseases, Peking University People’s Hospital, No. 11, Xizhimen South Street, Xicheng District, Beijing, 100044, China

    Yang Wang & Yulan Liu

Authors
  1. Yang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yulan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YL had the idea for the article; YW performed the literature search; YW and YL drafted the manuscript; and YL critically revised the manuscript.

Corresponding author

Correspondence to Yulan Liu.

Ethics declarations

Ethics Approval and Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, Y., Liu, Y. Neutrophil-Induced Liver Injury and Interactions Between Neutrophils and Liver Sinusoidal Endothelial Cells. Inflammation 44, 1246–1262 (2021). https://doi.org/10.1007/s10753-021-01442-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-021-01442-x

KEY WORDS

Search

Navigation