title: CD11b is protective in complement-mediated immune complex glomerulonephritis.
abstract: In chronic serum sickness, glomerular immune complexes form, yet C57BL/6 mice do not develop glomerulonephritis unless complement factor H (CfH) is absent, indicating the relevance of complement regulation. Complement receptor 3 (CD11b) and Fcγ receptors on leukocytes, and CfH on platelets, can bind immune complexes. Here we induced immune complex-mediated glomerulonephritis in CfH(-/-) mice chimeric for wild-type, CfH(-/-), CD11b(-/-), or FcRγ(-/-) bone marrow stem cells. Glomerulonephritis was worse in CD11b(-/-) chimeras compared with all others, whereas disease in FcRγ(-/-) and wild-type chimeras was comparable. Disease tracked strongly with humoral immune responses, but not glomerular immune complex deposits. Interstitial inflammation with M1 macrophages strongly correlated with glomerulonephritis scores. CD11b(-/-) chimeras had significantly more M1 macrophages and CD4(+) T cells. The renal dendritic cell populations originating from bone marrow-derived CD11c(+) cells were similar in all experimental groups. CD11b(+) cells bearing colony-stimulating factor 1 receptor were present in kidneys, including CD11b(-/-) chimeras; these cells correlated negatively with glomerulonephritis scores. Thus, experimental immune complex-mediated glomerulonephritis is associated with accumulation of M1 macrophages and CD4(+) T cells in kidneys and functional renal insufficiency. Hence, CD11b on mononuclear cells is instrumental in generating an anti-inflammatory response in the inflamed kidney.
authors.affiliation: Division of Nephrology, Department of Medicine, Clinical and Translational Research Center, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, USA.
authors.forename: Jessy J
authors.initials: JJ
authors.lastname: Alexander
authors.affiliation: Division of Nephrology, Department of Medicine, Clinical and Translational Research Center, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, USA.
authors.forename: Lee D
authors.initials: LD
authors.lastname: Chaves
authors.affiliation: Department of Pathology, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Chang
authors.affiliation: Division of Nephrology, Department of Medicine, Clinical and Translational Research Center, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Jacob
authors.affiliation: Division of Nephrology, Department of Medicine, Clinical and Translational Research Center, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Ritchie
authors.affiliation: Division of Nephrology, Department of Medicine, Clinical and Translational Research Center, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Quigg
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D001052:Apoferritins / Q000276:immunology; D001853:Bone Marrow / Q000378:metabolism; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism*; D005921:Glomerulonephritis / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D044087:Receptor, Anaphylatoxin C5a / Q000378:metabolism; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D012713:Serum Sickness / Q000150:complications
chemical_list: D000936:Antigen-Antibody Complex; D039481:CD11b Antigen; D018821:CD18 Antigens; D007074:Immunoglobulin G; D044087:Receptor, Anaphylatoxin C5a; D017452:Receptors, IgG; D017242:Complement Factor H; D001052:Apoferritins