title: MIP-1alpha and MCP-1 contribute to crescents and interstitial lesions in human crescentic glomerulonephritis.
abstract: BACKGROUND
  The precise molecular mechanisms of macrophage (Mphi) recruitment and activation in crescentic glomerulonephritis remain to be investigated. We hypothesized that locally produced macrophage inflammatory protein (MIP)-1alpha and monocyte chemoattractant protein (MCP)-1 via the chemokine receptors participate in the pathophysiology of human crescentic glomerulonephritis by recruiting and activating Mphi.
  
  
  METHODS
  We investigated the levels of MIP-1alpha and MCP-1 by enzyme-linked immunosorbent assay (ELISA) in 20 healthy subjects, 20 patients with crescentic glomerulonephritis, and 41 control patients with various other renal diseases. The presence of MIP-1alpha, MCP-1, and the cognate chemokine receptor for MIP-1alpha, CCR5, in the diseased kidneys was evaluated by immunohistochemical and in situ hybridization analyses.
  
  
  RESULTS
  MIP-1alpha-positive cells were mainly detected in crescentic lesions, whereas MCP-1 was mainly in the interstitium. In addition, we detected CCR5-positive cells in diseased glomeruli and interstitium. Urinary MIP-1alpha was detected in crescentic glomerulonephritis, even though it was below detectable levels in healthy subjects and in patients with other renal diseases without crescents. Urinary MIP-1alpha levels in the patients with crescentic glomerulonephritis were well correlated with the percentage of cellular crescents and the number of CD68-positive infiltrating cells and CCR5-positive cells in the glomeruli. However, urinary MCP-1 levels were well correlated with the percentage of both total crescents and fibrocellular/fibrous crescents and the number of CD68-positive infiltrating cells in the interstitium. Moreover, elevated urinary levels of both MIP-1alpha and MCP-1 dramatically decreased during glucocorticoid therapy-induced convalescence.
  
  
  CONCLUSIONS
  These observations suggest that locally produced MIP-1alpha may be involved in the development of cellular crescents in the acute phase via CCR5 and that MCP-1 may be involved mainly in the development of interstitial lesions in the chronic phase when fibrocellular/fibrous crescents are present, possibly through Mphi recruitment and activation.
authors.affiliation: First Department of Internal Medicine, School of Medicine, Kanazawa University, Japan. twada@med.kanazawa-u.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Wada
authors.forename: K
authors.initials: K
authors.lastname: Furuichi
authors.forename: C
authors.initials: C
authors.lastname: Segawa-Takaeda
authors.forename: M
authors.initials: M
authors.lastname: Shimizu
authors.forename: N
authors.initials: N
authors.lastname: Sakai
authors.forename: S I
authors.initials: SI
authors.lastname: Takeda
authors.forename: K
authors.initials: K
authors.lastname: Takasawa
authors.forename: H
authors.initials: H
authors.lastname: Kida
authors.forename: K I
authors.initials: KI
authors.lastname: Kobayashi
authors.forename: N
authors.initials: N
authors.lastname: Mukaida
authors.forename: Y
authors.initials: Y
authors.lastname: Ohmoto
authors.forename: K
authors.initials: K
authors.lastname: Matsushima
authors.forename: H
authors.initials: H
authors.lastname: Yokoyama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016375:Antisense Elements (Genetics) / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D005260:Female; D005921:Glomerulonephritis / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008181:Lupus Nephritis / Q000276:immunology; D008262:Macrophage Activation; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000378:metabolism
chemical_list: D016375:Antisense Elements (Genetics); D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D005938:Glucocorticoids; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5