title: Chemokine gene expression in anti-glomerular basement membrane antibody glomerulonephritis.
abstract: Chemokines may be important in the pathogenesis of glomerular leukocyte infiltration in antiglomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN). We studied the expression of the C-C chemokines [macrophage inflammatory protein (MIP)-1 alpha, monocyte chemotactic protein (MCP)-1, and RANTES] and C-X-C chemokines [platelet factor 4 (PF4), interferon-inducible protein of 10 kDa (IP-10), MIP-2, and cytokine-induced neutrophil chemoattractant (CINC)] at 30 min, 3, 6, 9, 15, and 24 h after induction of heterologous-phase anti-GBM Ab GN in Lewis rats. There was a rapid induction of CINC, MIP-2, MCP-1, and MIP-1 alpha mRNAs in the glomeruli of nephritic rats 30 min after administration of the anti-GBM Ab, whereas increases in PF4 and IP-10 mRNAs were not seen until 3 h. The mRNA expression of PF4, MIP-1 alpha, MIP-2, and IP-10 peaked at 3 h, whereas CINC and MCP-1 peaked at 6 and 15 h, respectively. By comparison, the expression of RANTES mRNA in rats with anti-GBM Ab GN did not differ from those of control rats. These changes in chemokine gene expression were associated with glomerular polymorphonuclear leukocytes (PMN) and monocyte/macrophage infiltration which peaked at 3 h (20.8 +/- 11.1 PMN/glomerulus) and 24 h (8.2 +/- 1.0 ED-1 cells/glomerulus), respectively. The administration of dexamethasone suppressed glomerular chemokine mRNA expression (60-98%) at both 3 and 15 h, which was associated with a 50-100% reduction in glomerular PMN and monocyte/macrophage infiltration, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anatomic Pathology, Amgen, Thousand Oaks, California 91320, USA.
authors.forename: W W
authors.initials: WW
authors.lastname: Tang
authors.forename: S
authors.initials: S
authors.lastname: Yin
authors.forename: A J
authors.initials: AJ
authors.lastname: Wittwer
authors.forename: M
authors.initials: M
authors.lastname: Qi
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001483:Base Sequence; D001485:Basement Membrane / Q000276:immunology*; D002465:Cell Movement; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics*; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression; D005921:Glomerulonephritis / Q000235:genetics* / Q000276:immunology*; D006133:Growth Substances / Q000276:immunology; D006706:Homeostasis; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats
chemical_list: D000906:Antibodies; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513296:Cxcl2 protein, rat; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D015335:Molecular Probes; D012333:RNA, Messenger; D003907:Dexamethasone