Skip to main content
Log in

Mast-cell secretion and angiogenesis, a quantitative study in rats and mice

  • Published:
Virchows Archiv B

Summary

The activation of the autogenous mast cells (MCs) in situ in intact mesenterial windows was elicited by the intraperitoneal injection of the MC secretagogue Compound 48/80 over a period of 1, 3 and 5 days in Sprague-Dawley rats and in C57 BL/6 and CBA/Ca mice. As a probe of MC secretion, the release of histamine was quantified fluorometrically at predetermined intervals during the treatment. Fourteen days after the start of the treatment, the angiogenic response was quantified histologically as the number of vessel profiles per unit length of mesenteric window. Both the MC-activating and the angiogenic effect of the 48/80-treatment was greater in the rats than in the mice. The occurrence of MC-mediated angiogenesis in the mouse is demonstrated here for the first time. In the rat, 48/80-induced MC mediated angiogenesis increased in a distinctly dose-dependent manner. Two daily doses of 48/80 was the most efficient angiogenic protocol tested; a single day’s treatment increased the number of vessels almost fivefold. The remarkable potency of the angiogenic reaction following MC secretion supports our previous notion that MC-mediated angiogenesis may have therapeutic implications in poorly vascularized tissues.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Atkins FM, Friedman MM, Subba Rao PV, Metcalfe DD (1985) Interactions between mast cells, fibroblasts and connective tissue components. Int Archs Allergy Appl Immun 77:96–102

    CAS  Google Scholar 

  • Bydlowski SP (1986) Mast cell: its mediators and effects on arterial wall metabolism. Gen Pharmacol 17:625–631

    PubMed  CAS  Google Scholar 

  • Castellot J Jr, Cochran D, Karnovsky M (1985) Effect of heparin on vascular smooth muscle cells. I. Cell metabolism. J Cell Physiol 124:21–28

    Article  PubMed  CAS  Google Scholar 

  • Dabbous MKh, Walker R, Haney L, Carter LM, Nicolson GL, Woolley DE (1986) Mast cell and matrix degradation at sites of tumour invasion in rat mammary adenocarcinoma. Br J Cancer 54:459–465

    PubMed  CAS  Google Scholar 

  • Douglas WW (1985) Histamine and 5-hydroxytryptamine (serotonin) and their antagonists. In: Gillman AG, Goodman LS, Rall TW, Murad F (eds) The pharmacological basis of therapeutics. MacMillan, New York, p 613

    Google Scholar 

  • Druvefors P, Norrby K (1988) Molecular aspects of mast-cellmediated mitogenesis in fibroblasts and mesothelial cells in situ. Virchows Arch [Cell Pathol] 55:187–192

    CAS  Google Scholar 

  • Enerbäck L, Norrby K (1989) The mast cells. In: Iversen OH (ed) Cell kinetics of the inflammatory reaction. Current topics in pathology, vol 79. Springer, New York, pp 169–204

    Google Scholar 

  • Ehrlich HP, Jung WK, Costa DE, Rajaratham JBM (1988) Effects of heparin on vascularization of artificial skin grafts in rats. Exp Mol Pathol 48:244–251

    Article  PubMed  CAS  Google Scholar 

  • Folkman J (1985a) Tumor angiogenesis. In: Klein G, Weinhouse S (eds) Advances in cancer research, vol 43. Academic Press, New York, pp 175–203

    Google Scholar 

  • Folkman J (1985b) Regulation of angiogenesis: a new function of heparin. Biochem Pharmacol 34:905–909

    Article  PubMed  CAS  Google Scholar 

  • Folkman J (1986) How is blood vessel growth regulated in normal and neoplastic tissue? —GHA Clowes memorial award lecture. Cancer Res 46:467–473

    PubMed  CAS  Google Scholar 

  • Folkman J, Klagsbrun M (1987) Angiogenic factors. Science 235:442–447

    Article  PubMed  CAS  Google Scholar 

  • Folkman J, Ingber DE (1987) Angiostatic steroids. Ann Surg 206:374–383

    Article  PubMed  CAS  Google Scholar 

  • Form DM, Pratt BM, Madri JA (1986) Endothelial cell proliferation during angiogenesis. In vitro modulation by basement membrane components. Lab Invest 55:521–530

    PubMed  CAS  Google Scholar 

  • Franzén L, Norrby K (1980) Local mitogenic effect of tissue mast cell secretion. Cell Tissue Kinet 13:635–642

    PubMed  Google Scholar 

  • Fraser RA, Simpson JG (1983) Role of mast cells in experimental tumour angiogenesis. In: Development of the vascular system. Ciba Foundation symposium 100. Pitman, London, pp 120–131

    Google Scholar 

  • Hatanaka K, Imakita M, Go S, Yamamoto A (1986) Effects of degranulation of mast cells on proliferation of mesenchymal cells in the mesentery of mice. Cell Tiss Res 246:53–56

    Article  CAS  Google Scholar 

  • Lindahl U, Pertoft H, Seljelid R (1979) Uptake and degradation of mast-cell granules by mouse peritoneal macrophages. Biochem J 182:189–193

    PubMed  CAS  Google Scholar 

  • Marks RM, Roche WR, Czerniecki M, Penny R, Nelson DS (1986) Mast cell granules cause proliferation of human microvascular endothelial cells. Lab Invest 55:289–294

    PubMed  CAS  Google Scholar 

  • Norrby K (1971) Effect of heparin, histamine and serotonin on the density-dependent inhibition of replication in two fibroblastic cell lines. Virchows Arch [Cell Pathol] 15:75–93

    Google Scholar 

  • Norrby K (1973) Effect of heparin on cell proliferation and kinetics in vitro ⊕n outline of a drug-testing scheme. In: Garattini S, Franchi G (eds) Chemotherapy of cancer dissemination and metastasis. Raven Press, New York, pp 269–277

    Google Scholar 

  • Norrby K (1980) Mast cell histamine, a local mitogen acting via H2 receptors in nearby tissue cells. Virchows Arch [Cell Pathol] 34:13–20

    CAS  Google Scholar 

  • Norrby K (1981) On the 48/80-induced secretion of tissue mast cells and its mitogenic effect on nearby cells in the intact rat. Virchows Arch [Cell Pathol] 38:13–20

    Article  Google Scholar 

  • Norrby K (1983) Intradermal mast-cell secretion causing cutaneous mitogenesis. Virchows Arch [Cell Pathol] 42:263–269

    CAS  Google Scholar 

  • Norrby K (1985) Evidence of mast-cell histamine being mitogenic in intact tissue. Agents Actions 16:287–290

    Article  PubMed  CAS  Google Scholar 

  • Norrby K, Eneström S (1984) Cellular and extracellular changes following mast-cell secretion in avascular rat mesentery. An electron-microscopic study. Cell Tiss Res 235:339–345

    Article  CAS  Google Scholar 

  • Norrby K, Enerbäck L, Franzén L (1976) Mast cell activation and tissue cell proliferation. Cell Tiss Res 170:289–303

    Article  CAS  Google Scholar 

  • Norrby K, Bergström S, Druvefors P (1983) Hyperplasia and growth of the true mesentery in the diabetic rat. APMIS (A) 91:195–202

    CAS  Google Scholar 

  • Norrby K, Bergström S, Druvefors P (1984) On disturbance of homeostasis in organ-cultured tissue. In Vitro 20:607–614

    Article  PubMed  CAS  Google Scholar 

  • Norrby K, Jakobsson A, Sörbo J (1986) Mast-cell-mediated angiogenesis: A novel experimental model using the rat mesentery. Virchows Arch [Cell Pathol] 52:195–206

    CAS  Google Scholar 

  • Norrby K, Jakobsson A, Sörbo J (1988) Age-dependent mastcell-mediated angiogenesis. APMIS [Suppl 2] 96:251–261

    Google Scholar 

  • Riley JF, West GB (1955) Histamine liberation in the rat and mouse. Arch Pharmacodyn 102:304–313

    CAS  Google Scholar 

  • Roche WR (1985 a) Mast cells and tumors. The specific enhancement of tumor proliferation in vitro. Am J Pathol 119:57–64

    PubMed  CAS  Google Scholar 

  • Roche WR (1985b) Mast cells and tumour angiogenesis: the tumour-mediated release of an endothelial growth factor from mast cells. Int J Cancer 36:721–728

    Article  PubMed  CAS  Google Scholar 

  • Schor AM, Schor SL (1983) Tumour angiogenesis. J Pathol 141:385–413

    Article  PubMed  CAS  Google Scholar 

  • Schwartz LB, Austen KF (1984) Structure and function of the chemical mediators of mast cells. Prog Allergy 34:271–321

    PubMed  CAS  Google Scholar 

  • Sholley MM, Ferguson GP, Seibel HR, Montour JL, Wilson JD (1984) Mechanisms of neovascularization. Vascular sprouting can occur without proliferation of endothelial cells. Lab Invest 51:624–634

    PubMed  CAS  Google Scholar 

  • Vallee BL, Riordan JF, Lobb RR, Higachi N, Fett JW, Crossley G, Bühler R, Budzik G, Breddam K, Bethune JL, Alderman EM (1985) Tumor-derived angiogenesis factors from rat Walker 256 carcinoma: an experimental investigation and review. Experientia 41:1–15

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This study was supported by the Swedish Medical Research Council, project 5942, and the king Gustav V Jubilee Clinic Cancer Research Foundation at Sahlgren’s Hospital

Rights and permissions

Reprints and permissions

About this article

Cite this article

Norrby, K., Jakobsson, A. & Sörbo, J. Mast-cell secretion and angiogenesis, a quantitative study in rats and mice. Virchows Archiv B Cell Pathol 57, 251–256 (1989). https://doi.org/10.1007/BF02899089

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02899089

Key words

Navigation