Endogenous CD100 promotes glomerular injury and macrophage recruitment in experimental crescentic glomerulonephritis.
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.
Li
Ming
M
Centre for Inflammatory Diseases, Monash University Department of Medicine, Clayton, Victoria, Australia.
O'Sullivan
Kim M
KM
Jones
Lynelle K
LK
Lo
Cecilia
C
Semple
Timothy
T
Kumanogoh
Atsushi
A
Kikutani
Hitoshi
H
Holdsworth
Stephen R
SR
Kitching
Richard
R
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*
D015703:Antigens, CD; C093224:CD100 antigen; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; C492118:Plxnb1 protein, mouse; D011956:Receptors, Cell Surface; D039961:Semaphorins
Kidney Int. 2002 Dec;62(6):2087-96
12427132
Am J Pathol. 2005 Nov;167(5):1207-19
16251406
J Am Soc Nephrol. 2005 Jul;16(7):2023-33
15888563
Kidney Int. 2003 Jan;63(1):83-95
12472771
Nat Rev Mol Cell Biol. 2005 Oct;6(10):789-800
16314868
J Immunol. 2001 Oct 15;167(8):4321-8
11591755
Kidney Int. 1989 Oct;36(4):537-44
2811060
Nat Immunol. 2008 Jan;9(1):17-23
18087252
Immunity. 2000 Nov;13(5):621-31
11114375
J Immunol. 2002 Aug 1;169(3):1175-81
12133937
Development. 2008 Oct;135(20):3333-43
18799546
Nat Rev Immunol. 2003 Feb;3(2):159-67
12563299
J Immunol. 1992 Jan 15;148(2):318-23
1530858
J Immunol. 2006 Sep 1;177(5):3406-12
16920982
J Am Soc Nephrol. 2000 Feb;11(2):262-269
10665933
J Immunol. 2000 Oct 15;165(8):4649-57
11035108
Blood. 2001 Jun 1;97(11):3498-504
11369643
J Immunol. 2004 Jul 1;173(1):136-44
15210767
J Am Soc Nephrol. 1999 Apr;10(4):752-9
10203359
Clin Exp Immunol. 1997 Jul;109(1):134-42
9218836
Kidney Int. 1990 Jul;38(1):86-95
2385089
J Am Soc Nephrol. 2004 Jul;15(7):1764-74
15213264
Cell. 1999 Oct 1;99(1):71-80
10520995
Int Immunol. 2003 Aug;15(8):1027-34
12882840
Kidney Int. 1997 Jan;51(1):94-103
8995722
Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11780-5
8876214
Immunity. 2000 Nov;13(5):633-42
11114376
J Exp Med. 2008 Jul 7;205(7):1673-85
18559453
J Immunol. 2006 Jun 1;176(11):6991-9
16709860
Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):674-8
8570614