CD11b is protective in complement-mediated immune complex glomerulonephritis

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.