Extrahepatic C6 is as effective as hepatic C6 in the generation of renal C5b-9 complexes.
In order to study the contribution of extrahepatic C6 to anti-Thy1.1 nephritis, C6 deficient PVG/c- livers were grafted in C6 sufficient PVG/c+ rats (Tx-L). Infusion of anti-Thy1.1 antibodies in Tx-L and PVG/c+ rats resulted in generation of C5b-9 complexes and subsequent glomerular injury, while infusion of anti-Thy1.1 antibodies in PVG/c- rats revealed no detectable C6 deposition. Because C6 mRNA was expressed in both liver and kidney tissue of PVG/c+ rats, we assessed whether production of C6 in the kidney alone was sufficient for glomerular injury. One kidney of a PVG/c- rat was replaced with a PVG/c+ kidney (Tx + K) followed by administration of anti-Thy1.1 antibodies. C6 deposits were detectable neither in PVG/c+ kidneys nor in PVG/c- kidneys of Tx + K rats, indicating that C6 production in PVG/c+ kidneys alone is not sufficient to contribute to renal injury. That C6 production had occurred was suggested by the presence of equal amounts C6 mRNA in control PVG/c+ kidneys and in grafted PVG/c+ kidneys of Tx + K rats. C6 mRNA expression in kidney tissue of PVG/c+ rats is presumably derived from peritubular sites. In conclusion, we have demonstrated that extrahepatic, but not renal synthesis of, C6 is sufficient to contribute to glomerular injury during anti-Thy1.1 nephritis.
Timmerman
J J
JJ
Department of Nephrology, University Hospital Leiden, The Netherlands.
van Dixhoorn
M G
MG
Schraa
E O
EO
van Gijlswijk-Janssen
D J
DJ
Muizert
Y
Y
Van ES
L A
LA
Daha
M R
MR
D000818:Animals; D015415:Biomarkers; D003175:Complement C2 / Q000172:deficiency; D003183:Complement C6 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015938:Complement Membrane Attack Complex / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D007668:Kidney / Q000378:metabolism*; D016030:Kidney Transplantation; D008099:Liver / Q000378:metabolism*; D016031:Liver Transplantation; D009393:Nephritis / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains / Q000097:blood; D012756:Sheep / Q000097:blood; D018800:Thy-1 Antigens / Q000276:immunology
D015415:Biomarkers; D003175:Complement C2; D003183:Complement C6; D015938:Complement Membrane Attack Complex; D012333:RNA, Messenger; D018800:Thy-1 Antigens