Abstract
Macromolecular leakage associated with mast cell degranulation was studied in the cremaster muscle microcirculation of copper-deficient rats. Male Sprague-Dawley rats were fed a purified diet either adequate for copper (6 μg copper/gram diet) or deficient (no added copper) 4 weeks prior to experimentation. The rats were anesthetized and the cremasters (with nerve and blood supply intact) were spread in a tissue bath filled with Kreb's solution.In vivo television microscopy was used to observe the microcirculation. Intravascular fluorescein isothiocyanate conjugated to bovine serum albumin was injected and interstitial fluorescent emission intensity was used as an index of macromolecular leakage. Topical administration of the mast cell degranulator compound 48/80 (1.0 and 10.0 μg/ml) induced a significantly greater macromolecular leakage in the copper-deficient animals. The compound 48/80 leakage was blocked in both groups of rats by pretreatment with diphenhydramine which is a histamine H1 receptor blocker. Topical administration of the inflammatory mediators histamine, serotonin, and bradykinin all induced macromolecular leakage which was not significantly different between groups. These results suggest that copper deficiency increases macromolecular leakage associated with mast cell degranulation by a primary effect on the mast cell rather than on the endothelium.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- CuA:
-
copper adequate diet
- CuD:
-
copper-deficient diet
References
R. A. Lewis and K. F. Austen,Mediation of local homeostasis and inflammation by leukotrienes and other mast cell-dependent compounds, Nature293, 103–108 (1981).
M. Ennis, S. E. Barrow and I. A. Blair,Prostaglandin and histamine release from stimulated rat peritoneal mast cells. Agents and Actions14, 397–400 (1984).
R. Milanino, A. Conforti, L. Franco, M. Marrella and G. Velo.Review: Copper and inflammation — a possible rationale for the pharmacological manipulation of inflammatory disorders. Agents and Actions16, 506–513 (1985).
A. J. Lewis,The role of copper in inflammatory disorders. Agents and Actions15, 513–519 (1984).
D. A. Schuschke, J. T. Saari, D. M. Ackermann and F. N. Miller,Microvascular responses in copper-deficient rats. Am. J. Physiol.257, H1607-H1612 (1989).
V. Kishore, B. Wokocha and L. Fourcade,Effect of nutritional copper deficiency on carrageenin edema in the rat. Biol. Trace Element Res.23, 97–107 (1990).
R. Milanino, S. Mazzoli, E. Passarella, G. Tarter and G. P. Velo,Carrageenan oedema in copper-deficient rats. Agents and Actions8, 618–622 (1978).
M. DiRosa, J. P. Giroud and D. A. Willoughby,Studies of the mediators of the acute inflammatory response induced in rats in different sites by carrageenan and turpentine. J. Pathol.104, 15–29 (1971).
W. D. M. Paton,Compound 48/80, a potent histamine liberator. Br. J. Pharmacol.6, 499–508 (1951).
Report of the American Institute of Nutrition Ad Hoc Committee on Standards for Nutritional Studies. J. Nutr.107, 1340–1348 (1977).
F. N. Miller, I. G. Joshua and G. L. Anderson,Quantitation of vasodilator-induced macromolecular leakage by in vivo fluorescent microscopy. Microvasc. Res.24, 56–67 (1982).
F. H. Nielsen, T. J. Zimmerman and T. R. Shuler,Interactions among nickel, copper, and iron in rats. Liver and plasma content of lipids and trace elements. Biol. Trace Element Res.4, 125–143 (1982).
W. T. Johnson and J. T. Saari,Temporal changes in heart size hematocrit and erythrocyte membrane protein in copper-deficient rats. Nutr. Res.11, 1403–1414 (1991).
K. G. D. Allen and L. M. Klevay,Cholesterolemia and cardiovascular abnormalities in rats caused by copper deficiency. Atherosclerosis29, 81–93 (1978).
H. A. Hunsacker, M. Morita and K. G. D. Allen,Marginal copper deficiency in rats. Aortal morphology of elastin and cholesterol values in first-generation adult males. Atherosclerosis51, 1–19 (1984).
J. R. Goodman, J. B. Warshaw and P. R. Dallman,Cardiac hypertrophy in rats with iron and copper deficiency: qualitative contribution of mitochondrial enlargement. Pediatr. Res.4, 244–256 (1970).
D. A. Schuschke, M. W. R. Reed, J. T. Saari and F. N. Miller,Copper deficiency alters vasodilation in the rat cremaster muscle microcirculation. J. Nutr.122, 1547–1552 (1992).
M. J. White, F. N. Miller, L. S. Heuser and C. G. Pietsch,Human malignant ascites and histamine-induced protein leakage from the normal microcirculation. Microvasc. Res.35, 63–72 (1988).
S. J. Galli,New concepts about the mast cell. N. Engl. J. Med.328, 257–265 (1993).
Y. Kitamura,Heterogeneity of mast cells and phenotypic change between subpopulations. Ann. Rev. Immunol.7, 59–76 (1989).
R. F. Del Maestro, J. Björk and K.-E. Arfors,Increase microvascular permeability induced by enzymatically genera free radicals. II. Role of superoxide anion radical, hydrogen peroxide, and hydroxyl radical. Microvasc. Res.22, 255–270 (1981).
P. F. Mannaioni and E. Masini,The release of histamine by free radicals. Free Radical Biol. Med.5, 177–197 (1988).
C. A. Owen,Biochemical Aspects of Copper. InCopper Proteins, Ceruloplasmin, and Copper Protein Binding, pp. 9–17, 75–111, 128–176. Noyes, Park Ridge, NJ 1982.
Author information
Authors and Affiliations
Additional information
This material is based upon work supported by the Cooperative State Research Service, U.S. Department of Agriculture, under Agreement No. 92-37200-7676. Mention of a trademark of proprietary product does not constitute a guarantee or warranty of the product by the U.S. Department of Agriculture, and does not imply its approval to the exclusion of other products that may also be suitable.
Rights and permissions
About this article
Cite this article
Schuschke, D.A., Saari, J.T. & Miller, F.N. The role of the mast cell in acute inflammatory responses of copper-deficient rats. Agents and Actions 42, 19–24 (1994). https://doi.org/10.1007/BF02014294
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02014294