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.
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
Bydlowski SP (1986) Mast cell: its mediators and effects on arterial wall metabolism. Gen Pharmacol 17:625–631
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
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
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
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
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
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
Folkman J (1985a) Tumor angiogenesis. In: Klein G, Weinhouse S (eds) Advances in cancer research, vol 43. Academic Press, New York, pp 175–203
Folkman J (1985b) Regulation of angiogenesis: a new function of heparin. Biochem Pharmacol 34:905–909
Folkman J (1986) How is blood vessel growth regulated in normal and neoplastic tissue? —GHA Clowes memorial award lecture. Cancer Res 46:467–473
Folkman J, Klagsbrun M (1987) Angiogenic factors. Science 235:442–447
Folkman J, Ingber DE (1987) Angiostatic steroids. Ann Surg 206:374–383
Form DM, Pratt BM, Madri JA (1986) Endothelial cell proliferation during angiogenesis. In vitro modulation by basement membrane components. Lab Invest 55:521–530
Franzén L, Norrby K (1980) Local mitogenic effect of tissue mast cell secretion. Cell Tissue Kinet 13:635–642
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
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
Lindahl U, Pertoft H, Seljelid R (1979) Uptake and degradation of mast-cell granules by mouse peritoneal macrophages. Biochem J 182:189–193
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
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
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
Norrby K (1980) Mast cell histamine, a local mitogen acting via H2 receptors in nearby tissue cells. Virchows Arch [Cell Pathol] 34:13–20
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
Norrby K (1983) Intradermal mast-cell secretion causing cutaneous mitogenesis. Virchows Arch [Cell Pathol] 42:263–269
Norrby K (1985) Evidence of mast-cell histamine being mitogenic in intact tissue. Agents Actions 16:287–290
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
Norrby K, Enerbäck L, Franzén L (1976) Mast cell activation and tissue cell proliferation. Cell Tiss Res 170:289–303
Norrby K, Bergström S, Druvefors P (1983) Hyperplasia and growth of the true mesentery in the diabetic rat. APMIS (A) 91:195–202
Norrby K, Bergström S, Druvefors P (1984) On disturbance of homeostasis in organ-cultured tissue. In Vitro 20:607–614
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
Norrby K, Jakobsson A, Sörbo J (1988) Age-dependent mastcell-mediated angiogenesis. APMIS [Suppl 2] 96:251–261
Riley JF, West GB (1955) Histamine liberation in the rat and mouse. Arch Pharmacodyn 102:304–313
Roche WR (1985 a) Mast cells and tumors. The specific enhancement of tumor proliferation in vitro. Am J Pathol 119:57–64
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
Schor AM, Schor SL (1983) Tumour angiogenesis. J Pathol 141:385–413
Schwartz LB, Austen KF (1984) Structure and function of the chemical mediators of mast cells. Prog Allergy 34:271–321
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
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
Author information
Authors and Affiliations
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
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02899089