THE ROLE OF THE MAST-CELL IN ACUTE INFLAMMATORY RESPONSES OF COPPER-DEFICIENT RATS

Macromolecular leakage associated with mast cell degranulation was stu died in the cremaster muscle microcirculation of copper-deficient rats . Male Sprague-Dawley rats were fed a purified diet either adequate fo r copper (6 mu g copper/gram diet) or deficient (no added copper) 4 we eks prior to experimentation. The rats were anesthetized and the crema sters (with nerve and blood supply intact) were spread in a tissue bat h filled with Kreb's solution. In vivo television microscopy was used to observe the microcirculation. Intravascular fluorescein isothiocyan ate conjugated to bovine serum albumin was injected and interstitial f luorescent emission intensity was used as an index of macromolecular l eakage. Topical administration of the mast cell degranulator compound 48/80 (1.0 and 10.0 mu g/ml) induced a significantly greater macromole cular leakage in the copper-deficient animals. The compound 48/80 leak age was blocked in both groups of rats by pretreatment with diphenhydr amine which is a histamine H-1 receptor blocker. Topical administratio n of the inflammatory mediators histamine, serotonin, and bradykinin a ll induced macromolecular leakage which was not significantly differen t between groups. These results suggest that copper deficiency increas es macromolecular leakage associated with mast cell degranulation by a primary effect on the mast cell rather than on the endothelium.