INHIBITION OF THE ALTERNATIVE PATHWAY OF COMPLEMENT BY GLOMERULAR CHONDROITIN SULFATE 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.