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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:164-171.)
© 1997 American Heart Association, Inc.

Articles

Complement C5b-9 Increases Plasminogen Binding and Activation on Human Endothelial Cells

Victoria J. Christiansen; Peter J. Sims; Karen K. Hamilton

the Department of Medicine and William K. Warren Medical Research Institute, University of Oklahoma Health Sciences Center, Oklahoma City, and the Blood Research Institute of the Blood Center of Southeastern Wisconsin (P.J.S.), Milwaukee.

Correspondence to Victoria J. Christiansen, PhD, BSEB Rm 306, University of Oklahoma Health Sciences Center, PO Box 26901, Oklahoma City, OK 73190. E-mail vicki.christiansen@cclink.net.UOKHSC.edu.

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 (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 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.

Key Words: fibrinolysis • complement 9 • plasmin • von Willebrand factor • carboxypeptidase

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