MAST-CELL MODULATION OF MACROPHAGE PROCOAGULANT ACTIVITY AND TNF PRODUCTION

The expression of surface procoagulants by macrophages represents an i mportant mechanism underlying local fibrin deposition at sites of extr avascular inflammation. Mast cells by virtue of their perivascular loc ation are in a potent position to influence the inflammatory process. The present studies investigated the role of the mast cell in the gene ration of macrophage procoagulant activity (PCA) and tumor necrosis fa ctor (TNF) production. Mast cell lysates caused a marked induction of macrophage PCA (dose and time dependent) and TNF release while whole m ast cells had little effect. This effect was prevented by the tyrosine kinase inhibitor herbimycin. At the molecular level, Northern blot an alysis revealed marked induction of the murine macrophage tissue facto r transcript in response to incubation with mast cell lysate compared to control. These studies thus suggest that mast cell-macrophage inter actions promote macrophage-mediated fibrin deposition and TNF release and that this effect is in part mediated via induction of tyrosine pho sphorylation. These observations suggest novel mechanisms of involveme nt of the mast cell in the inflammatory microenvironment and macrophag e activation. (C) 1995 Academic Press, Inc.