title: Accumulation of immune complexes in glomerular disease is independent of locally synthesized c3.
abstract: Although complement activation can make immune complex glomerulonephritis worse, the third complement component also can solubilize immune complexes and thus reduce the severity of disease. How C3 that is produced within the kidney contributes to this balance is unknown. This study therefore investigated the relative roles of systemic and local C3 production in a model of glomerular immune complex disease. Injection of sheep anti-glomerular basement membrane antibody into preimmunized mice resulted in accumulation of immune complexes and progressive loss of function over 14 d that was much more marked in C3-deficient (C3-/-) mice. In C3-sufficient mice that received a transplant of a C3-/- mouse kidney and in C3-/- mice with C3-sufficient mouse kidney transplants, the severity and the pattern of injury went with the complement status of the recipient. That is, mice with deficient circulating C3 developed severe glomerular immune complex disease, whereas those with a high level of circulating C3 had well-preserved glomerular structure and function. It is concluded that circulating C3 is a critical factor in reducing the glomerular accumulation of immune complexes. Local synthesis of C3 did not have a major influence on this aspect of glomerular disease.
authors.affiliation: Department of Nephrology and Transplantation, Guy's Hospital, King's College London, UK. neil.sheerin@kcl.ac.uk
authors.forename: Neil S
authors.initials: NS
authors.lastname: Sheerin
authors.forename: Katsushige
authors.initials: K
authors.lastname: Abe
authors.forename: Paul
authors.initials: P
authors.lastname: Risley
authors.forename: Steven H
authors.initials: SH
authors.lastname: Sacks
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001323:Autoantibodies; D001707:Biopsy, Needle; D003176:Complement C3 / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism / Q000473:pathology*; D007105:Immune Complex Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D007677:Kidney Function Tests; D051379:Mice; D008810:Mice, Inbred C57BL; D011336:Probability; D012680:Sensitivity and Specificity
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D003176:Complement C3; C051951:antiglomerular basement membrane antibody