title: The C5a receptor has a key role in immune complex glomerulonephritis in complement factor H-deficient mice.
abstract: Chronic serum sickness leads to the formation of glomerular immune complexes; however, C57BL/6 mice do not develop glomerulonephritis unless complement factor H (CFH) is absent from the plasma. Here we studied the role for C5a receptor (R) in this setting. The exaggerated humoral immune response in CFH(-/-) mice was normalized in CFH(-/-)C5aR(-/-) double knockout mice, highlighting the C5aR dependence. The CFH knockout mice developed proliferative glomerulonephritis with endocapillary F4/80+ macrophage infiltration, a process reduced in the double knockout mice. There was no interstitial inflammation by histologic criteria or flow cytometry for F4/80+ Ly6C(hi)CCR2(hi) inflammatory macrophages. There were, however, more interstitial CD3+ CD4+ T lymphocytes in CFH knockout mice with chronic serum sickness, while double knockout mice had greater than 5-fold more Ly6C(lo)CCR2(lo) anti-inflammatory macrophages compared to the CFH knockout mice. Mice lacking C5aR were significantly protected from functional renal disease as assessed by blood urea nitrogen levels. Thus, IgG- and iC3b-containing immune complexes are not inflammatory in C57BL/6 mice. Yet when these mice lack CFH, sufficient C3b persists in glomeruli to generate C5a and activate C5aR.
authors: Section of Nephrology, Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA. jalexand@medicine.bsd.uchicago.edu
authors: Jessy J
authors: JJ
authors: Alexander
authors: Lee
authors: L
authors: Chaves
authors: Anthony
authors: A
authors: Chang
authors: Richard J
authors: RJ
authors: Quigg
mesh_terms: D000818:Animals; D017242:Complement Factor H / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000081208:Hereditary Complement Deficiency Diseases; D007105:Immune Complex Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007668:Kidney / Q000276:immunology / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044087:Receptor, Anaphylatoxin C5a / Q000235:genetics* / Q000276:immunology*; D012713:Serum Sickness / Q000235:genetics / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D015432:Glomerulonephritis, Membranoproliferative
chemical_list: D044087:Receptor, Anaphylatoxin C5a; D017242:Complement Factor H