Inhibition of the alternative pathway of complement by glomerular chondroitin sulphate proteoglycan.
Cultured rat glomerular epithelial cells (GEC) synthesize and secrete a complement inhibitory chondroitin sulphate B proteoglycan (termed GCRF). As proteoglycans and their component glycosaminoglycans may affect several different steps of complement activation, the functional properties of GCRF were investigated in this study. GCRF inhibited preformed alternative pathway convertases (C3bBbP), but did not substantially accelerate their decay. In contrast to other polyanions, GCRF did not affect the activity of human or rat factor H, nor did it inhibit the terminal complement proteins. GCRF inhibited the effect of decay-accelerating factor (DAF) on C3bBbP when the two were incubated together and DAF was in excess, but it did not affect the decay of DAF of classical pathway convertases. However, when DAF was first incorporated into the erythrocyte membrane, the effect of GCRF on C3bBbP was additive to that of DAF. Thus, GCRF inhibits the activity of C3bBbP and blocks the action of DAF, but not that of factor H, perhaps by binding to factor B in the alternative pathway convertase.
Quigg
R J
RJ
Department of Internal Medicine, Medical College of Virginia, Richmond 23298.
D000818:Animals; D018958:CD55 Antigens; D011508:Chondroitin Sulfate Proteoglycans / Q000494:pharmacology*; D050577:Complement C3-C5 Convertases / Q000187:drug effects; D003169:Complement Inactivator Proteins / Q000187:drug effects; D015938:Complement Membrane Attack Complex / Q000187:drug effects; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D003171:Complement Pathway, Classical / Q000187:drug effects; D005340:Fibrinogen; D007678:Kidney Glomerulus / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000187:drug effects; D051381:Rats
D018958:CD55 Antigens; D011508:Chondroitin Sulfate Proteoglycans; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex; D008562:Membrane Glycoproteins; D005340:Fibrinogen; D050577:Complement C3-C5 Convertases