title: Expression of the chemokine monocyte chemoattractant protein-1 and its receptor chemokine receptor 2 in human crescentic glomerulonephritis.
abstract: Crescents are morphologic manifestations of severe glomerular injury. Several chemokines and their receptors have been demonstrated to be involved in animal models of crescentic glomerulonephritis (cGN) and are potential targets for therapeutic interventions. Therefore, the expression of monocyte chemoattractant protein-1 (MCP-1), its receptor chemokine receptor 2B (CCR2B), and CCR5 in human cGN was studied. MCP-1 and CCR2B mRNA expression was evaluated, by in situ hybridization, in serial sections of 23 renal biopsies from patients with cGN. T cells, macrophages, and CCR5-expressing cells were examined by immunohistochemical analysis. MCP-1 mRNA was expressed by cells in crescents, parietal epithelium, and tubular epithelium, as well as by infiltrating leukocytes in the tubulointerstitium. The expression of CCR2B mRNA was observed in cells in glomeruli and crescents and in infiltrating leukocytes in the tubulointerstitium. CCR2B mRNA expression could not be clearly localized to intrinsic renal cells; evidence that most of the CCR2B-expressing cells were leukocytes is provided. CD3-positive T cells formed the major part of the interstitial cell infiltrates but were rare within the glomerular tufts. CD68-positive macrophages constituted a major population of infiltrating cells in crescents and contributed significantly to the interstitial infiltrates. The number of glomerular macrophages was associated with the number of MCP-1- and CCR2B-positive glomerular cells. Expression of CCR2B was significantly correlated with interstitial CD3-positive T cells. CCR5 expression was restricted to infiltrating leukocytes and was correlated quantitatively and by localization with interstitial CD3-positive T cells and CD68-positive macrophages. These first morphologic data on the distribution of CCR2-positive cells in human cGN suggest differential effects of chemokines and their receptors on the distribution of infiltrating leukocytes in different compartments of the kidney.
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington.
authors.forename: Stephan
authors.initials: S
authors.lastname: Segerer
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Hudkins
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington.
authors.forename: Tracy
authors.initials: T
authors.lastname: Goodpaster
authors.affiliation: Medizinische Klinik II, Klinikum der Rheinisch-Westfaelischen Technischen Hoshschule, Aachen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Eitner
authors.affiliation: Medizinische Poliklinik, Klinikum der Universitaet, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
authors.affiliation: Medizinische Poliklinik, Klinikum der Universitaet, Munich, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Schlöndorff
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Alpers
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D002452:Cell Count; D018932:Chemokine CCL2 / Q000378:metabolism*; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000473:pathology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D018932:Chemokine CCL2; D012333:RNA, Messenger; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; C515334:CCR2 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule