title: Loss of CD11b exacerbates murine complement-mediated tubulointerstitial nephritis.
abstract: Acute complement activation occurs in the tubulointerstitium (TI) of kidneys transplanted from Crry(-/-)C3(-/-) mice into complement-sufficient wildtype mice, followed by marked inflammatory cell infiltration, tubular damage and interstitial fibrosis. We postulated iC3b-CD11b interactions were critical in this TI nephritis model. We transplanted Crry(-/-)C3(-/-) mouse kidneys into CD11b(-/-) and wildtype C57BL/6 mice. Surprisingly, there was greater inflammation in Crry(-/-)C3(-/-) kidneys in CD11b(-/-) recipients compared to those in wildtype hosts. Kidneys in CD11b(-/-) recipients had large numbers of CD11b-Ly6ChiCCR2hiF4/80+ cells consistent with inflammatory (M1) macrophages recruited from circulating monocytes of the host CD11b(-/-) animal. There was also an expanded population of CD11b(+)CD11c(+)Ly6C(-)F4/80(hi) cells. Since these cells were CD11b(+), they must have originated from the transplanted kidney; their surface protein expression and appearance within the kidney were consistent with the intrinsic renal mononuclear cellular population. These cells were markedly expanded relative to all relevant controls, including the contralateral donor kidney and Crry(-/-)C3(-/-) mouse kidneys in CD11b(+/+) wildtype recipients. Direct evidence for their in situ proliferation was the presence of nuclear Ki67 and PCNA in CD11b(+)F4/80(+) cells. Thus, in this experimental model in which there is unrestricted C3 activation, CD11b(+) monocytes limit their own infiltration into the kidney and prevent proliferation of endogenous mononuclear cells. This suggests a role for outside-in iC3b-CD11b signals in limiting intrinsic organ inflammation.
authors.affiliation: Division of Nephrology, Department of Medicine, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, United States of America.
authors.forename: Lee Daniel
authors.initials: LD
authors.lastname: Chaves
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Lihua
authors.initials: L
authors.lastname: Bao
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, The University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Anthony
authors.initials: A
authors.lastname: Chang
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Haas
authors.affiliation: Division of Nephrology, Department of Medicine, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, United States of America.
authors.forename: Richard John
authors.initials: RJ
authors.lastname: Quigg
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism*; D003179:Complement C3b / Q000172:deficiency / Q000378:metabolism*; D016030:Kidney Transplantation; D051379:Mice; D009000:Monocytes / Q000378:metabolism; D009395:Nephritis, Interstitial / Q000097:blood / Q000378:metabolism* / Q000601:surgery; D011951:Receptors, Complement / Q000172:deficiency; D017463:Receptors, Complement 3b
chemical_list: D039481:CD11b Antigen; C081470:Cr1l protein, mouse; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D003179:Complement C3b