Skip to main content

Advertisement

SpringerLink
Log in

Angiostatin inhibits activation and migration of neutrophils

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

There is a critical need to identify molecules that modulate the biology of neutrophils because activated neutrophils, though necessary for host defense, cause exuberant tissue damage through production of reactive oxygen species and increased lifespan. Angiostatin, an endogenous anti-angiogenic cleavage product of plasminogen, binds to integrin αvβ3, ATP synthase and angiomotin and its expression is increased in inflammatory conditions. We test the hypothesis that angiostatin inhibits neutrophil activation, induces apoptosis and blocks recruitment in vivo and in vitro. The data show immuno-reactivity for plasminogen/angiostatin in resting neutrophils. Angiostatin conjugated to FITC revealed that angiostatin was endocytozed by activated mouse and human neutrophils in a lipid raft-dependent fashion. Co-immunoprecipitation of human neutrophil lysates, confocal microscopy of isolated mouse and human neutrophils and functional blocking experiments showed that angiostatin complexes with flotillin-1 along with integrin αvβ3 and ATP synthase. Angiostatin inhibited fMLP-induced neutrophil polarization, as well as caused inhibition of hsp-27 phosphorylation and stabilization of microtubules. Angiostatin treatment, before or after LPS-induced neutrophil activation, inhibited phosphorylation of p38 and p44/42 MAPKs, abolished reactive oxygen species production and released the neutrophils from suppressed apoptosis, as indicated by expression of activated caspase-3 and morphological evidence of apoptosis. Finally, intravital microscopy and myeloperoxidase assay showed inhibition of neutrophil recruitment in post-capillary venules of TNFα-treated cremaster muscle in mouse. These in vitro and in vivo data demonstrate angiostatin as a broad deactivator and silencer of neutrophils and an inhibitor of their migration. These data potentially open new avenues for the development of anti-inflammatory drugs.

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • Allen L-AH (2007) Immunofluorescence and confocal microscopy of neutrophils. Methods Mol Biol 412:273–287

    Article  CAS  PubMed  Google Scholar 

  • Amulic B, Cazalet C, Hayes GL, Metzler KD, Zychlinsky A (2012) Neutrophil function: from mechanisms to disease. Annu Rev Immunol 30:459–489

    Article  CAS  PubMed  Google Scholar 

  • Aoshiba K, Yasui S, Hayashi M, Tamaoki J, Nagai A (1999) Role of p38-mitogen-activated protein kinase in spontaneous apoptosis of human neutrophils. J Immunol 162:1692–1700

    CAS  PubMed  Google Scholar 

  • Artoni A, Li J, Mitchell B, Ruan J, Takagi J, Springer TA, French DL, Coller BS (2004) Integrin beta 3 regions controlling binding of murine mAb 7E3: implications for the mechanism of integrin alphaIIbbeta3 activation. Proc Natl Acad Sci U S A 101:13114–13120

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Barreiro O, De La Fuente H, Mittelbrunn M, Sánchez-Madrid F (2007) Functional insights on the polarized redistribution of leukocyte integrins and their ligands during leukocyte migration and immune interactions. Immunol Rev 218:147–164

    Article  CAS  PubMed  Google Scholar 

  • Barreiro O, Martín P, González-Amaro R, Sánchez-Madrid F (2010) Molecular cues guiding inflammatory responses. Cardiovasc Res 86:174–182

    Article  CAS  PubMed  Google Scholar 

  • Benelli R, Morini M, Carrozzino F, Ferrari N, Minghelli S, Santi L, Cassatella M, Noonan DM, Albini A (2002) Neutrophils as a key cellular target for angiostatin: implications for regulation of angiogenesis and inflammation. FASEB J 16:267–269

    CAS  PubMed  Google Scholar 

  • Bradley ME, Bond ME, Manini J, Brown Z, Charlton SJ (2009) SB265610 is an allosteric, inverse agonist at the human CXCR2 receptor. Br J Pharmacol 158:328–338

    Article  CAS  PubMed  Google Scholar 

  • Castel S, Pagan R, Mitjans F, Piulats J, Goodman S, Jonczyk A, Huber F, Vilaro S, Reina M (2001) RGD peptides and monoclonal antibodies, antagonists of alpha(v)-integrin, enter the cells by independent endocytic pathways. Lab Invest 81:1615–1626

    Article  CAS  PubMed  Google Scholar 

  • Chavakis T, Athanasopoulos A, Rhee JS, Orlova V, Schmidt-Woll T, Bierhaus A, May AE, Celik I, Nawroth PP, Preissner KT (2005) Angiostatin is a novel anti-inflammatory factor by inhibiting leukocyte recruitment. Blood 105:1036–1043

    Article  CAS  PubMed  Google Scholar 

  • Dudani AK, Ben-Tchavtchavadze M, Porter S, Tackaberry E (2005) Angiostatin and plasminogen share binding to endothelial cell surface actin. Biochem Cell Biol 83:28–35

    Article  CAS  PubMed  Google Scholar 

  • Dudani AK, Mehic J, Martyres A (2007) Plasminogen and angiostatin interact with heat shock proteins. Mol Cell Biochem 300:197–205

    Article  CAS  PubMed  Google Scholar 

  • Eddy RJ, Pierini LM, Maxfield FR (2002) Microtubule asymmetry during neutrophil polarization and migration. Mol Biol Cell 13:4470–4483

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ernkvist M, Birot O, Sinha I, Veitonmaki N, Nystrom S, Aase K, Holmgren L (2008) Differential roles of p80- and p130- angiomotin in the switch between migration and stabilization of endothelial cells. Biochim Biophys Acta, Mol Cell Res 1783:429–437

    Article  CAS  PubMed  Google Scholar 

  • Ernkvist M, Persson NL, Audebert S, Lecine P, Sinha I, Liu M, Schlueter M, Horowitz A, Aase K, Weide T, Borg JP, Majumdar A, Holmgren L (2009) The Amot/Patj/Syx signaling complex spatially controls RhoA GTPase activity in migrating endothelial cells. Blood 113:244–253

    Article  CAS  PubMed  Google Scholar 

  • Espinosa A, Leiva A, Peña M, Müller M, Debandi A, Hidalgo C, Angélica Carrasco M, Jaimovich E (2006) Myotube depolarization generates reactive oxygen species through NAD(P)H oxidase; ROS-elicited Ca2+ stimulates ERK, CREB, early genes. J Cell Phys 209:379–388

    Article  CAS  Google Scholar 

  • Fabbri M, Di Meglio S, Gagliani MC, Consonni E, Molteni R, Bender JR, Tacchetti C, Pardi R (2005) Dynamic partitioning into lipid rafts controls the endo-exocytic cycle of the alphaL/beta2 integrin, LFA-1, during leukocyte chemotaxis. Mol Biol Cell 16:5793–5803

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fialkow L, Wang Y, Downey GP (2007) Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Free Radic Biol Med 42:153–164

    Article  CAS  PubMed  Google Scholar 

  • Gagne V, Moreau J, Plourde M, Lapointe M, Lord M, Gagnon E, Fernandes MJ (2009) Human angiomotin-like 1 associates with an angiomotin protein complex through its coiled-coil domain and induces the remodeling of the actin cytoskeleton. Cell Motil Cytoskeleton 66:754–768

    Article  CAS  PubMed  Google Scholar 

  • Hamacher J, Lucas R, Lijnen HR, Buschke S, Dunant Y, Wendel A, Grau GE, Suter PM, Ricou B (2002) Tumor necrosis factor-{alpha} and angiostatin are mediators of endothelial cytotoxicity in bronchoalveolar lavages of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 166:651

    Article  PubMed  Google Scholar 

  • Harris ES, Shigeoka AO, Li W, Adams RH, Prescott SM, McIntyre TM, Zimmerman GA, Lorant DE (2001) A novel syndrome of variant leukocyte adhesion deficiency involving defects in adhesion mediated by beta1 and beta2 integrins. Blood 97:767–776

    Article  CAS  PubMed  Google Scholar 

  • Hendey B, Lawson M, Marcantonio EE, Maxfield FR (1996) Intracellular calcium and calcineurin regulate neutrophil motility on vitronectin through a receptor identified by antibodies to integrins αv and β3. Blood 87:2038–2048

    CAS  PubMed  Google Scholar 

  • Hermel M, Dailey W, Hartzer MK (2010) Efficacy of plasmin, microplasmin, and streptokinase-plasmin complex for the in vitro degradation of fibronectin and laminin- implications for vitreoretinal surgery. Curr Eye Res 35:419–424

    Article  CAS  PubMed  Google Scholar 

  • Hino M, Hosoya H (2003) Small heat shock protein Hsp27 directly binds to alpha/beta tubulin heterodimer and inhibits DMSO-induced tubulin polymerization. Biomed Res 24:27–30

    CAS  Google Scholar 

  • Hino M, Kurogi K, Okubo MA, Murata-Hori M, Hosoya H (2000) Small heat shock protein 27 (HSP27) associates with tubulin/microtubules in HeLa cells. Biochem Biophys Res Commun 271:164–169

    Article  CAS  PubMed  Google Scholar 

  • Insall RH (2010) Understanding eukaryotic chemotaxis: a pseudopod-centred view. Nat Rev Mol Cell Biol 11:453–458

    Article  CAS  PubMed  Google Scholar 

  • Insall RH, Machesky LM (2009) Actin dynamics at the leading edge: from simple machinery to complex networks. Dev Cell 17:310–322

    Article  CAS  PubMed  Google Scholar 

  • Jog NR, Jala VR, Ward RA, Rane MJ, Haribabu B, McLeish KR (2007) Heat shock protein 27 regulates neutrophil chemotaxis and exocytosis through two independent mechanisms. J Immunol 178:2421–2428

    CAS  PubMed  Google Scholar 

  • Jurasz P, Santos-Martinez MJ, Radomska A, Radomski MW (2006) Generation of platelet angiostatin mediated by urokinase plasminogen activator: effects on angiogenesis. J Thromb Haemost 4:1095–1106

    Article  CAS  PubMed  Google Scholar 

  • Kenan DJ, Wahl ML (2005) Ectopic localization of mitochondrial ATP synthase: a target for anti-angiogenesis intervention? J Bioenerg Biomembr 37:461

    Article  CAS  PubMed  Google Scholar 

  • Khan AI, Heit B, Andonegui G, Colarusso P, Kubes P (2005) Lipopolysaccharide: a p38 MAPK-dependent disrupter of neutrophil chemotaxis. Microcirc 12:421–432

    Article  CAS  Google Scholar 

  • Kuijpers TW, Van Lier RA, Hamann D, de Boer M, Thung LY, Weening RS, Verhoeven AJ, Roos D (1997) Leukocyte adhesion deficiency type 1 (LAD-1)/variant. A novel immunodeficiency syndrome characterized by dysfunctional beta2 integrins. J Clin Invest 100:1725–1733

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kutsuna H, Suzuki K, Kamata N, Kato T, Hato F, Mizuno K, Kobayashi H, Ishii M, Kitagawa S (2004) Actin reorganization and morphological changes in human neutrophils stimulated by TNF, GM-SCF and G-CSF: The role of MAP kinases. Am J Physiol Cell Physiol 286:C55–C64

    Article  CAS  PubMed  Google Scholar 

  • Lammermann T, Bader BL, Monkley SJ, Worbs T, Wedlich-Soldner R, Hirsch K, Keller M, Forster R, Critchley DR, Fassler R, Sixt M (2008) Rapid leukocyte migration by integrin-independent flowing and squeezing. Nature 453:51–55

    Article  PubMed  Google Scholar 

  • Lawson MA, Maxfield FR (1995) Ca2 + − and calcineurin-dependent recycling of an integrin to the front of migrating neutrophils. Nature 377:75–79

    Article  CAS  PubMed  Google Scholar 

  • Lee TY, Muschal S, Pravda EA, Folkman J, Abdollahi A, Javaherian K (2009) Angiostatin regulates the expression of antiangiogenic and proapoptotic pathways via targeted inhibition of mitochondrial proteins. Blood 114:1987–1998

    Article  CAS  PubMed  Google Scholar 

  • Ley K, Laudanna C, Cybulsky MI, Nourshargh S (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7:678–689

    Article  CAS  PubMed  Google Scholar 

  • Liu L, Kubes P (2003) Molecular mechanisms of leukocyte recruitment: organ-specific mechanisms of action. Thromb Haemost 89:213–220

    CAS  PubMed  Google Scholar 

  • Liu L, Aerbajinai W, Ahmed SM, Rodgers GP, Angers S, Parent CA (2012) Radil controls neutrophil adhesion and motility through beta2-integrin activation. Mol Biol Cell 23:4751–4765

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lokuta MA, Huttenlocher A (2005) TNF-α promotes a stop signal that inhibits neutrophil polarization and migration via a p38 MAPK pathway. J Leukoc Biol 78:210–219

    Article  CAS  PubMed  Google Scholar 

  • Lucas R, Lijnen HR, Suffredini AF, Pepper MS, Steinberg KP, Martin TR, Pugin J (2002) Increased angiostatin levels in bronchoalveolar lavage fluids from ARDS patients and from human volunteers after lung instillation of endotoxin. Thromb Haemost 87:966–971

    CAS  Google Scholar 

  • Markvicheva KN, Gorokhovatskii AY, Mishina NM, Mudrik NN, Vinokurov LM, Luk’Yanov SA, Belousov VV (2010) Signaling function of phagocytic NADPH oxidase: activation of MAP kinase cascades in phagocytosis. Russ J Bioorg Chem 36:124–129

    Article  CAS  Google Scholar 

  • Moon C, Han JR, Park HJ, Hah JS, Kang JL (2009) Synthetic RGDS peptide attenuates lipopolysaccharide-induced pulmonary inflammation by inhibiting integrin signaled MAP kinase pathways. Respir Res 10:18

    Article  PubMed Central  PubMed  Google Scholar 

  • Mustafa S, See HB, Seeber RM, Armstrong SP, White CW, Ventura S, Ayoub MA, Pfleger KD (2012) Identification and profiling of novel alpha1A-adrenoceptor-CXC chemokine receptor 2 heteromer. J Biol Chem 287:12952–12965

    Article  CAS  PubMed  Google Scholar 

  • Niggli V (2003) Signaling to migration in neutrophils: importance of localized pathways. Int J Biochem Cell Biol 35:1619–1638

    Article  CAS  PubMed  Google Scholar 

  • Nuzzi PA, Lokuta MA, Huttenlocher A (2007) Analysis of neutrophil chemotaxis. Methods Mol Biol 370:23–36

    Article  CAS  PubMed  Google Scholar 

  • O’Mahony CA, Seidel A, Albo D, Chang H, Tuszynski GP, Berger DH (1998) Angiostatin generation by human pancreatic cancer. J Surg Res 77:55–58

    Article  PubMed  Google Scholar 

  • Perri SR, Annabi B, Galipeau J (2007a) Angiostatin inhibits monocyte/macrophage migration via disruption of actin cytoskeleton. FASEB J 21:3928

    Article  CAS  PubMed  Google Scholar 

  • Perri SR, Martineau D, Francois M, Lejeune L, Bisson L, Durocher Y, Galipeau J (2007b) Plasminogen Kringle 5 blocks tumor progression by antiangiogenic and proinflammatory pathways. Mol Cancer Therap 6:441–449

    Article  CAS  Google Scholar 

  • Pluskota E, Soloviev DA, Szpak D, Weber C, Plow EF (2008) Neutrophil apoptosis: selective regulation by integrin αMβ2 ligands. J Immunol 181:3609–3619

    CAS  PubMed Central  PubMed  Google Scholar 

  • Puzon-McLaughlin W, Kamata T, Takada Y (2000) Mutliple discontinuous ligand-mimetic antibody binding sites define a ligand-binding pocket in integrin alpha(IIb)beta3. J Biol Chem 275:7795–7802

    Article  CAS  PubMed  Google Scholar 

  • Rainger GE, Buckley CD, Simmons DL, Nash GB (1999) Neutrophils sense flow-generated stress and direct their migration through αVβ3-integrin. Am J Physiol Heart Circ Physiol 276:H858–H864

    CAS  Google Scholar 

  • Sabroe I, Dower SK, Whyte MK (2005) The role of Toll-like receptors in the regulation of neutrophil migration, activation and apoptosis. Clin Infect Dis 41:S421–S426

    Article  CAS  PubMed  Google Scholar 

  • Scapini P, Nesi L, Morini M, Tanghetti E, Belleri M, Noonan D, Presta M, Albini A, Cassatella MA (2002) Generation of biologically active angiostatin kringle 1–3 by activated human neutrophils 1. J Immunol 168:5798–5804

    CAS  PubMed  Google Scholar 

  • Schierwagen C, Bylund-Fellenius AC, Lundberg C (1990) Improved method for quantification of tissue PMN accumulation measured by myeloperoxidase activity. J Pharm Meth 23:179–186

    Article  CAS  Google Scholar 

  • Sharma MR, Rothman V, Tuszynski GP, Sharma MC (2006) Antibody-directed targeting of angiostatin’s receptor annexin II inhibits Lewis Lung Carcinoma tumor growth via blocking of plasminogen activation: possible biochemical mechanism of angiostatin’s action. Exp Mol Pathol 81:136–145

    Article  CAS  PubMed  Google Scholar 

  • Singh B, Fu C, Bhattacharya J (2000) Vascular expression of the αvβ3-integrin in lung and other organs. Am J Physiol Lung Cell Mol Physiol 278:217–226

    Google Scholar 

  • Singh B, Janardhan KS, Kanthan R (2005) Expression of angiostatin, integrin αvβ3, and vitronectin in human lungs in sepsis. Exp Lung Res 31:771–782

    Article  CAS  PubMed  Google Scholar 

  • Singh RD, Marks DL, Holicky EL, Wheatley CL, Kaptzan T, Sato SB, Kobayashi T, Ling K, Pagano RE (2010) Gangliosides and β1-integrin are required for caveolae and membrane domains. Traffic 11:348–360

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Spisani S, Falzarano S, Traniello S, Nalli M, Selvatici R (2005) A ‘pure’ chemoattractant formylpeptide analogue triggers a specific signalling pathway in human neutrophil chemotaxis. FEBS J 272:883–891

    Article  CAS  PubMed  Google Scholar 

  • Syed SP, Martin AM, Haupt HM, Arenas-Elliot CP, Brooks JJ (2007) Angiostatin receptor annexin II in vascular tumors including angiosarcoma. Hum Pathol 38:508–513

    Article  CAS  PubMed  Google Scholar 

  • Tabruyn SP, Griffioen AW (2007) Molecular pathways of angiogenesis inhibition. Biochem Biophys Res Commun 355:1–5

    Article  CAS  PubMed  Google Scholar 

  • Tarui T, Miles LA, Takada Y (2001) Specific interaction of angiostatin with integrin alpha(v)beta(3) in endothelial cells. J Biol Chem 276:39562–39568

    Article  CAS  PubMed  Google Scholar 

  • Troyanovsky B, Levchenko T, Mansson G, Matvijenko O, Holmgren L (2001) Angiomotin an angiostatin binding protein that regulates endothelial cell migration and tube formation. J Cell Biol 152:1247–1254

    Article  CAS  PubMed  Google Scholar 

  • Tsukada H, Ying X, Fu C, Ishikawa S, McKeown-Longo P, Albelda S, Bhattacharya S, Bray BA, Bhattacharya J (1995) Ligation of endothelial alpha v beta 3 integrin increases capillary hydraulic conductivity of rat lung. Circ Res 77:651–659

    Article  CAS  PubMed  Google Scholar 

  • Tuluc F, Meshki J, Kunapuli SP (2003) Membrane lipid microdomains differentially regulate intracellular signaling events in human neutrophils. Int Immunopharmacol 3:1775–1790

    Article  CAS  PubMed  Google Scholar 

  • Underwood DC, Osborn RR, Bochnowicz S, Webb EF, Rieman DJ, Lee JC, Romanic AM, Adams JL, Hay DWP, Griswold DE (2000) SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung. Am J Physiol Lung Cell Mol Physiol 279:L895–L902

    CAS  PubMed  Google Scholar 

  • Wahl ML, Kenan DJ, Gonzalez-Gronow M, Pizzo SV (2005) Angiostatin’s molecular mechanism: aspects of specificity and regulation elucidated. J Cell Biochem 96:242–261

    Article  CAS  PubMed  Google Scholar 

  • Warejcka DJ, Twining SS (2005) Specific conformational changes of plasminogen induced by chloride ions, 6-aminohexanoic acid and benzamidine, but not the overall openness of plasminogen regulate, production of biologically active angiostatins. Biochem J 392:703–712

    Article  CAS  PubMed  Google Scholar 

  • Wells CD, Fawcett JP, Traweger A, Yamanaka Y, Goudreault M, Elder K, Kulkarni S, Gish G, Virag C, Lim C (2006) A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells. Cell 125:535–548

    Article  CAS  PubMed  Google Scholar 

  • Wenzel-Seifert K, Hurt CM, Seifert R (1998) High constitutive activity of the human formyl peptide receptor. J Biol Chem 273:24181–24189

    Article  CAS  PubMed  Google Scholar 

  • Westphal JR, Van’t Hullenaar R, Geurts-Moespot A, Sweep FCJG, Verheijen JH, Bussemakers MMG, Askaa J, Clemmensen I, Eggermont AAM, Ruiter DJ, De Waal RMW (2000) Angiostatin generation by human tumor cell lines: Involvement of plasminogen activators. Int J Cancer 86:760–767

    Article  CAS  PubMed  Google Scholar 

  • Witko-Sarsat V (2010) Apoptosis, cell death and inflammation. J Innate Immunity 2:201–203

    Article  Google Scholar 

  • Witko-Sarsat V, Rieu P, Descamps-Latscha B, Lesavre P, Halbwachs-Mecarelli L (2000) Neutrophils: molecules, functions and pathophysiological aspects. Lab Invest 80:617–654

    Article  CAS  PubMed  Google Scholar 

  • Wong CHY, Heit B, Kubes P (2010) Molecular regulators of leucocyte chemotaxis during inflammation. Cardiovasc Res 86:183–191

    Article  CAS  PubMed  Google Scholar 

  • Yan SR, Novak MJ (1999) Diverse effects of neutrophil integrin occupation on respiratory burst activation. Cell Immunol 195:119–126

    Article  CAS  PubMed  Google Scholar 

  • Yoo SK, Lam PY, Eichelberg MR, Zasadil L, Bement WM, Huttenlocher A (2012) The role of microtubules in neutrophil polarity and migration in live zebrafish. J Cell Sci 125:5702–5710

    Article  CAS  PubMed  Google Scholar 

  • Zhong B, Jiang K, Gilvary DL, Epling-Burnette EK, Ritchey C, Liu J, Jackson RJ, Hong-Geller E, Wei S (2003) Human neutrophils utilize a Rac/Cdc42-dependent MAPK pathway to direct intracellular granule mobilization toward ingested microbial pathogens. Blood 101:3240–3248

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Dr. Wolfgang Kuebler for providing valuable comments on the manuscript and Mr. Daryoush Hajinezhad for technical assistance with the confocal microscope. The study was funded through a grant from the Natural Sciences and Engineering Research Council of Canada to Dr. Baljit Singh. Dr. Aulakh was supported through a Dean’s Scholarship from the College of Graduate Studies and Research, University of Saskatchewan.

Authorship

G.K.A., L.L. and B.S. planned the experiments, analyzed data and wrote the manuscript. G.K.A. carried out all the experiments. Y.B. helped in angiostatin post-treatment confocal experiments on human neutrophils.

Author information

Authors and Affiliations

  1. Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, SK, S7N 5B4, Canada

    Gurpreet K. Aulakh, Yadu Balachandran & Baljit Singh

  2. Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada

    Lixin Liu

Authors
  1. Gurpreet K. Aulakh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yadu Balachandran
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lixin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Baljit Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Baljit Singh.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(JPEG 87 kb)

High Resolution Image (TIFF 1647 kb)

ESM 2

(JPEG 45 kb)

High Resolution Image (TIFF 718 kb)

ESM 3

(JPEG 23 kb)

High Resolution Image (TIFF 81 kb)

(WMV 1439 kb)

(WMV 4345 kb)

(MOV 3951 kb)

(MOV 4558 kb)

(MOV 3734 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aulakh, G.K., Balachandran, Y., Liu, L. et al. Angiostatin inhibits activation and migration of neutrophils. Cell Tissue Res 355, 375–396 (2014). https://doi.org/10.1007/s00441-013-1753-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-013-1753-0

Keywords

Search

Navigation