Human glomerular epithelial cells synthesize and secrete the third component of complement.
Complement proteins in serum are mainly synthesized by hepatocytes. Recently, 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 epithelial cells (GEC). Using reverse transcriptase polymerase reaction, we have found that GEC and whole kidney expressed the C3 mRNA for C3. By ELISA, we have found that C3 was secreted in culture supernatants harvested from cultured GEC. The secretion of C3 is regulated by proinflammatory 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 upregulation by proinflammatory cytokines may suspect a role in local activation of complement which may lead to glomerular injury. We further studied the expression of C3 step regulatory proteins (membrane cofactor 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 beta and TGF-beta. These results indicate that the expression of these regulatory proteins is tissue specific and may be implicated in inflammatory processes.
Moutabarrik
A
A
Department of Nephrology, Faculty of Medicine, Casablanca, Morocco.
Nakanishi
I
I
Matsumoto
M
M
Zaid
D
D
Seya
T
T
D015703:Antigens, CD / Q000096:biosynthesis; D001483:Base Sequence; D018958:CD55 Antigens; D003176:Complement C3 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase
D015703:Antigens, CD; C497857:CD46 protein, human; D018958:CD55 Antigens; D003176:Complement C3; D016207:Cytokines; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012194:RNA-Directed DNA Polymerase