Differential effects of cytomegalovirus infection on complement synthesis by human mesangial cells.
Viruses may be eliminated by the host immune system via complement-mediated lysis of infected cells. Previously, we have demonstrated that the synthesis of complement factor B by renal mesangial cells (MC) is enhanced by interferon-alpha (IFN-alpha), -beta and -gamma. In the present study we investigate the effect of human cytomegalovirus (HCMV) infection on the production of complement factors by MC. The production of factor B, C2, C4 and factor H by mock-infected MC was 0.2 +/- 0.4, 3.9 +/- 6.8, 1.7 +/- 0.8 and 149 +/- 36 ng/10(6) cells per 72 h, respectively. In HCMV-infected MC cultures an induction of both factor B and C2 protein synthesis was observed up to 2.2 +/- 1.1 and 156 +/- 74 ng/10(6) cells per 72 h, respectively. The synthesis of C4 and factor H of 2.9 +/- 2.0 and 146 +/- 31 ng/10(6) cells, respectively, was not altered significantly. By Northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis it was demonstrated that factor B and C2 mRNA expression were up-regulated in HCMV-infected cell cultures, whereas the levels of C4 and factor H mRNA were not changed. When MC cultures were inoculated with heat- or UV-inactivated HCMV no enhancement of factor B mRNA expression was observed. The enhanced expression was not blocked by phosphono acetic acid (PAA), suggesting that expression of the HCMV immediate early or early genes is sufficient to induce complement synthesis. We conclude that infection of MC cultures with HCMV selectively induces complement C2 and factor B production, probably mediated by interferons.
Timmerman
J J
JJ
Department of Nephrology, University Hospital Leiden, The Netherlands.
Beersma
M F
MF
van Gijlswijk-Janssen
D J
DJ
van Es
L A
LA
van der Woude
F J
FJ
Daha
M R
MR
D015152:Blotting, Northern; D002478:Cells, Cultured; D003175:Complement C2 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D011415:Complement Factor B / Q000378:metabolism; D017242:Complement Factor H / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D003587:Cytomegalovirus / Q000528:radiation effects; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000166:cytology; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D010746:Phosphonoacetic Acid / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014466:Ultraviolet Rays; D015854:Up-Regulation
C493495:CFH protein, human; D003175:Complement C2; D003181:Complement C4; D012333:RNA, Messenger; D017242:Complement Factor H; D003165:Complement System Proteins; D007372:Interferons; D011415:Complement Factor B; D010746:Phosphonoacetic Acid