HUMAN GLOMERULAR EPITHELIAL-CELLS SYNTHESIZE AND SECRETE THE 3RD COMPONENT OF COMPLEMENT

Complement proteins in serum are mainly synthesized by hepatocytes. Re cently, many cell types have been reported to synthesize complement in various tissues. In this study, we report the synthesis and secretion of the third component of complement (C3) by cultured glomerular epit helial cells (GEC). Using reverse transcriptase polymerase reaction, w e have found that GEC and whole kidney expressed the C3 mRNA for C3. B y ELISA, we have found that C3 was secreted in culture supernatants ha rvested from cultured GEC. The secretion of C3 is regulated by proinfl ammatory cytokines (IL-1 beta, TNF-alpha and IL-6). IL-1 beta is shown to be the most potent stimulator of C3 secretion from GEC. The exact significance of C3 produced at glomerular site is not clear, but its u pregulation by proinflammatory cytokines may suspect a role in local a ctivation of complement which may lead to glomerular injury. We furthe r studied the expression of C3 step regulatory proteins (membrane cofa ctor protein (MCP), decay-accelerating factor (DAF), CR-1 and CD59 (a terminal step regulatory protein) by cultured GEC. Treatment of GEC by proinflammatory cytokines IL-1 beta, TGF-beta, TNF-alpha and IL-6 did not modify the expression of MCP, DAF and CR-1 whereas an increase in the expression of CD59 could be observed after treatment with IL-1 be ta and TGF-beta. These results indicate that the expression of these r egulatory proteins is tissue specific and may be implicated in inflamm atory processes.