Mast Cell Modulation of Macrophage Procoagulant Activity and TNF Production

Abstract

The expression of surface procoagulants by macrophages represents an important mechanism underlying local fibrin deposition at sites of extravascular inflammation. Mast cells by virtue of their perivascular location are in a potent position to influence the inflammatory process. The present studies investigated the role of the mast cell in the generation of macrophage procoagulant activity (PCA) and tumor necrosis factor (TNF) production. Mast cell lysates caused a marked induction of macrophage PCA (dose and time dependent) and TNF release while whole mast cells had little effect. This effect was prevented by the tyrosine kinase inhibitor herbimycin. At the molecular level, Northern blot analysis revealed marked induction of the murine macrophage tissue factor transcript in response to incubation with mast cell lysate compared to control. These studies thus suggest that mast cell-macrophage interactions promote macrophage-mediated fibrin deposition and TNF release and that this effect is in part mediated via induction of tyrosine phosphorylation. These observations suggest novel mechanisms of involvement of the mast cell in the inflammatory microenvironment and macrophage activation.