TERMINAL COMPLEMENT PROTEINS C5B-9 RELEASE BASIC FIBROBLAST GROWTH-FACTOR AND PLATELET-DERIVED GROWTH-FACTOR FROM ENDOTHELIAL-CELLS

Interactions between endothelium and vascular smooth muscle cells play a major role in the biology of the blood vessel wall. Growth factors released from endothelial cells control in part the normal and patholo gical proliferation of vascular smooth muscle cells. Endothelial depos its of C5b-9 proteins, the membrane attack complex of complement (MAC) , have been found in a variety of pathological tissues in which cell p roliferation is an early characteristic abnormality, including atheros clerosis. We have explored a possible bridging role for terminal compl ement C5b-9 proteins in eliciting focal signals for cell proliferation by releasing growth factors from endothelial cells. We found that bot h bovine aortic and human umbilical vein cells respond to the MAC by r eleasing basic fibroblast growth factor and platelet-derived growth fa ctor. These mitogens stimulate DNA synthesis in Swiss 3T3, vascular sm ooth muscle, and glomerular mesangial cells. Based on these findings, we propose that complement-induced release of mitogens from endothelia l cells is a novel pathogenic mechanism for proliferative disorders.