title: Endogenous CD100 promotes glomerular injury and macrophage recruitment in experimental crescentic glomerulonephritis.
abstract: CD100 participates in adaptive immune responses and is important in neural cell migration. To determine the role of endogenous CD100 in severe glomerular inflammation, we induced experimental crescentic glomerulonephritis by planting a foreign antigen in glomeruli of sensitized normal and CD100-deficient (CD100(-/-)) mice. Fewer CD100(-/-) glomeruli exhibited crescent formation or severe histological changes. Antigen-specific immune responses were reduced in CD100(-/-) mice. There was less interferon (IFN)-gamma and interleukin (IL)-4 production by splenocytes and fewer activated T and B cells were present in lymph nodes of immunized CD100(-/-) mice. Serum antigen-specific immunoglobulin (IgG) levels were also decreased. Glomerular macrophage and CD4(+) cell infiltration, and IgG and C3 deposition were attenuated. Normal kidneys expressed mRNA for CD100 and plexin-B1 (the tissue receptor of CD100). Direct immunofluorescence showed that renal-CD100 protein was predominantly in tubules, while plexin-B1 was present in both glomeruli and tubules. To determine whether glomerular plexin-B1 mediates leucocyte recruitment via leucocyte CD100, recruitment was studied after passive transfer of heterologous antibody (attracting neutrophils) or isologous antibody (attracting macrophages). Glomerular macrophages were reduced in CD100(-/-) mice, but neutrophil recruitment was equivalent, consistent with CD100 expression on macrophages, but not neutrophils. CD100 promotes severe nephritogenic immune responses and leucocyte CD100-glomerular plexin-B1 interactions enhance macrophage recruitment to glomeruli.
authors.affiliation: Centre for Inflammatory Diseases, Monash University Department of Medicine, Clayton, Victoria, Australia.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Kim M
authors.initials: KM
authors.lastname: O'Sullivan
authors.forename: Lynelle K
authors.initials: LK
authors.lastname: Jones
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lo
authors.forename: Timothy
authors.initials: T
authors.lastname: Semple
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kikutani
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Holdsworth
authors.forename: Richard
authors.initials: R
authors.lastname: Kitching
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D018450:Disease Progression; D050533:Glomerular Basement Membrane / Q000276:immunology; D005921:Glomerulonephritis / Q000276:immunology*; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis; D007678:Kidney Glomerulus / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D011956:Receptors, Cell Surface / Q000378:metabolism; D039961:Semaphorins / Q000276:immunology*
chemical_list: D015703:Antigens, CD; C093224:CD100 antigen; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; C492118:Plxnb1 protein, mouse; D011956:Receptors, Cell Surface; D039961:Semaphorins
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