Degranulation of human mast cells induces an endothelial antigen central to leukocyte adhesion

To understand better the role of mast cell secretory products in the genesis of inflammation, a system was developed for in vitro degranulation of human mast cells in skin organ cultures. Within 2 hr after morphine sulfate-induced degranulation, endothelial cells lining microvessels adjacent to affected mast cells expressed an activation antigen important for endothelial-leukocyte adhesion. Identical results were obtained when other mast cell secretagogues (anti-IgE, compound 48/80, and calcium ionophore A23187) were used. Induction of this antigen was abrogated by preincubation with cromolyn sodium, an inhibitor of mast cell secretion, and by antiserum to tumor necrosis factor alpha. These findings indicate that degranulation of mast cells activates dermal endothelium through tumor necrosis factor-dependent mechanisms. This event may be critical to the elicitation phase of cutaneous inflammation.