Mast cell activation induces P-selectin-dependent leukocyte rolling and adhesion in postcapillary venules in vivo.

As studied by intravital microscopy, local challenge with the mast cell secretagogue compound 48/80 was found to increase the leukocyte rolling fraction, decrease rolling velocity and induce firm leukocyte adhesion in postcapillary venules of the rat mesentery. These effects of compound 48/80 were inhibited by a monoclonal anti-P-selectin antibody, but not by combined treatment with H1 and H2 histamine-receptor antagonists. Moreover, the response to compound 48/80 was not mimicked by exogenous histamine or 5-hydroxytryptamine (5-HT). These novel findings indicate that mediator(s) other than histamine and 5-HT evoke P-selectin-dependent leukocyte rolling and thereby promote firm leukocyte adhesion in mast cell-dependent inflammation.