COMPLEMENT COMPONENT C7 IS A PLASMINOGEN-BINDING PROTEIN

Ab deposition, whether by reaction with the specific Ag or by preforme d immune complexes, is followed by activation and deposition of comple ment components. Tissue destruction is observed in the Ab- and complem ent-induced lesions. The proteolytic enzyme plasmin is thought to part icipate in the Ab- and complement-mediated organ pathology. Plasmin is generated from plasma-derived plasminogen by cell-derived plasminogen activators (PAs). Two types of PAs are known, urokinase-type PA (uPA) and tissue-type PA (tPA). We investigated whether the PA system and t he complement system can interact to promote local plasmin generation. Among the terminal complement components C5b6, C7, C8, and C9, the no nenzymatic component C7 is a plasminogen-binding protein. Radioligand binding studies revealed that the isolated component, as well as C7 af ter its incorporation into the terminal complement complex C5b-9, can bind plasminogen. Binding was inhibited by the lysine analogues 6-amin ohexanoic acid and tranexamic acid, implicating the lysine binding sit es of plasminogen into the binding interaction. tPA-mediated plasminog en activation was enhanced in the presence of C7. Based on these findi ngs, an interaction is proposed between the complement system and the plasminogen activator system; a mechanism that may focus plasmin activ ity to structures that have been tagged by Ab and complement depositio n.