Depression of phagocytosis by plasmin degradation products of plasma fibronectin.

Previous research has shown that disseminated intravascular coagulation causes a depression in RE function. Fibronectin, a high-molecular-weight surface-binding glycoprotein, is known to modulate RE function by facilitating opsonic activity and is sensitive to proteolytic cleavage by plasmin, yielding FNDP. The present investigation suggests that isolated FNDP, generated in vitro by incubation with plasmin, can depress phagocytosis in vivo as well as in vitro. Phagocytosis in rats was determined by a clearance technique employing CR51-RBCs and in vitro by employing a monolayer of peritoneal exudate macrophages. The in vivo studies demonstrated significantly reduced hepatic phagocytosis after the injection of FNDP an delayed clearance of injected test particles. Macrophage uptake in vitro, supported by either normal rat serum or purified fibronectin, was significantly reduced when incubated with FNDP. These results suggest that depression of the RE system and phagocytosis during intravascular coagulation may be mediated in part by the formation of plasmin degradation products of plasma fibronectin.