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 pathological proliferation of vascular smooth muscle cells. Endothelial deposits of C5b-9 proteins, the membrane attack complex of complement (MAC), have been found in a variety of pathological tissues in which cell proliferation is an early characteristic abnormality, including atherosclerosis. We have explored a possible bridging role for terminal complement C5b-9 proteins in eliciting focal signals for cell proliferation by releasing growth factors from endothelial cells. We found that both bovine aortic and human umbilical vein cells respond to the MAC by releasing basic fibroblast growth factor and platelet-derived growth factor. These mitogens stimulate DNA synthesis in Swiss 3T3, vascular smooth muscle, and glomerular mesangial cells. Based on these findings, we propose that complement-induced release of mitogens from endothelial cells is a novel pathogenic mechanism for proliferative disorders.
Benzaquen
L R
LR
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Nicholson-Weller
A
A
Halperin
J A
JA
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D015938:Complement Membrane Attack Complex / Q000494:pharmacology* / Q000502:physiology; D017077:Culture Media, Conditioned; D004247:DNA / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis*; D051381:Rats; D014471:Umbilical Veins
D015938:Complement Membrane Attack Complex; D017077:Culture Media, Conditioned; D010982:Platelet-Derived Growth Factor; D016222:Fibroblast Growth Factor 2; D004247:DNA