Antigen-antibody complexes enhance the production of complement component C3 by human mesangial cells.
Deposition of immune complexes (ICX), with or without complement, occurs in various forms of glomerulonephritis. It has been reported that upregulation of complement C3 mRNA expression is found in kidneys of patients with ICX glomerulonephritis. In vitro studies have indicated that mesangial cells (MC) synthesize C3. Furthermore, MC express Fc gammaRIII receptors. This study investigates whether ICX alter C3 and factor H production by MC. MC were cultured in medium alone or in medium with insoluble heat-aggregated rat IgG (AIgG) or with insoluble ICX. Basal production of C3 and factor H was 10 +/- 1 ng/10(6) and 605 +/- 15 ng/10(6) cells, respectively. The presence of 400 microg/ml AIgG or ICX resulted in upregulation of C3 production to 999 +/- 15 ng/10(6) and 510 +/- 1 ng/10(6) cells, respectively, whereas no significant change in factor H production was observed. The upregulation of C3 was inhibitable by cycloheximide, suggesting that de novo protein synthesis was required. By reverse transcription PCR and Northern blot analysis, it was demonstrated that C3 and interleukin-6 mRNA expression was upregulated in MC after incubation with AIgG. No detectable change in factor H mRNA expression was seen. In conclusion, it is shown that incubation of MC with AIgG or ICX not only results in upregulated production of inflammatory mediators such as cytokines, but also leads to an upregulation of C3 synthesis. Therefore, it is hypothesized that ICX deposited within the mesangium may enhance the local production of C3 via interaction with Fc receptors on MC.
Timmerman
J J
JJ
Department of Nephrology, University Hospital Leiden, The Netherlands.
Van Gijlswijk-Janssen
D J
DJ
Van Der Kooij
S W
SW
Van Es
L A
LA
Daha
M R
MR
D000199:Actins / Q000235:genetics; D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001483:Base Sequence; D002478:Cells, Cultured; D003176:Complement C3 / Q000096:biosynthesis* / Q000235:genetics; D017242:Complement Factor H / Q000096:biosynthesis / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005920:Glomerular Mesangium / Q000276:immunology* / Q000378:metabolism; D005921:Glomerulonephritis / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism; D011112:Polymyxin B / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017452:Receptors, IgG / Q000235:genetics
D000199:Actins; D000936:Antigen-Antibody Complex; C493495:CFH protein, human; D003176:Complement C3; D017931:DNA Primers; D007074:Immunoglobulin G; D012333:RNA, Messenger; D017452:Receptors, IgG; D017242:Complement Factor H; D011112:Polymyxin B