Complement C5b-9 increases plasminogen binding and activation on human endothelial cells.
Deposition of the terminal complement proteins (C5b-9) on human endothelial cells can result in cell lysis or nonlytic alterations of cell function including procoagulant responses. Because regulation of fibrinolysis is a central endothelial function and because C9 contains a carboxyl-terminal lysine similar to other proteins that bind and facilitate activation of plasminogen (PG), the effects of complement injury on PG binding and activation on these cells were investigated. Activation of complement through deposition of C5b67 complexes on endothelial cells resulted in a small increase (approximately 20%) in PG binding. Incorporation of C8 into C5b-8 resulted in no further increase in binding; however, specific 125I-PG binding was increased by approximately 100% after C5b-9 deposition. Moreover, PG was found to bind specifically to C7 and C9. The PG bound to endothelial cells after C5b-9 deposition was readily activated by tissue-type plasminogen activator (TPA). In a cell-free system, complement C9 and a synthetic peptide composed of the 20 carboxyl-terminal amino acids of C9 enhanced PG activation by TPA. Removal of the carboxyl-terminal lysine of C9 abolished the enhancement of PG activation without diminishing PG binding. We conclude that membrane C9 may comprise a binding site for PG and serve to enhance activation of this zymogen by TPA. These findings suggest that immune injury to the endothelium may enhance both the fibrin-generating and fibrinolytic capacity of the vessel wall.
Christiansen
V J
VJ
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA. vicki.christiansen@cclink.net.UOKHSC.edu
Sims
P J
PJ
Hamilton
K K
KK
D001665:Binding Sites; D002478:Cells, Cultured; D015938:Complement Membrane Attack Complex / Q000378:metabolism* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D010958:Plasminogen / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism* / Q000494:pharmacology
D015938:Complement Membrane Attack Complex; D010958:Plasminogen; D010960:Plasminogen Activators