Release of Fibrinolytic Enzymes by Macrophages in Response to Soluble Fibrin
In previous data (J. Exp. Med. 147:76,1977), we have demonstrated that soluble fibrin/fibrinogen complexes are bound to the plasma membrane of guinea pig peritoneal macrophages. This binding is largely irreversible and is not a result of phagocytosis. We have extended our studies to examine the response in vitro of peritoneal macrophages to soluble fibrin/fibrinogen complexes. Unstimulated mouse macrophages were collected by peritoneal lavage and 5–60 μg of soluble fibrin/fibrinogen complexes placed into tissue culture dishes containing the unstimulated cells. Aliquots of the media were collected at 24, 48 and 72 hours. The cell-free media contained increasing amounts both of plasminogen activator and an enzymatic activity which resulted in fibrin and fibrinogen proteolysis independent of the amount of plasmingoen present. The major proteolytic activity was due to the non-plasminogen dependent enzyme. Similar enzymes were released from peritoneal macrophages stimulated in vivo. The plasminogen activator enzyme had a low molecular weight comparable to that previously reported by Unkeless et al, with in vivo stimulation. Other coagulation moieties, such as plasmin and α-2 macroglobulin plasmin complexes did not result in release of the macrophage proteolytic enzymes. The results suggest that the previously described release of fibrinolytic enzymes after thioglycolate injections, may also result from the more pathophysiological stimulation by soluble fibrin/fibrinogen complexes. Release of these enzymes from phagocytic cells may be important, not only in blood clearance of soluble fibrin/fibrinogen complexes, but as part of thrombus reabsorption and wound healing.