title: Chemokine and chemokine receptor expression during initiation and resolution of immune complex glomerulonephritis.
abstract: Chemokines participate in leukocyte infiltration, which plays a major role in glomerular injury during immune complex glomerulonephritis (IC-GN). Because target cell expression of chemokine receptors (CCR) is thought to mediate leukocyte migration, the expression pattern of chemokines and CCR in a model of IC-GN was examined. The transient course and predominant glomerular pathology of this model allows the examination of both the induction and resolution phases of IC-GN. GN was induced in mice by daily apoferritin injection for 2 wk. Urine samples and kidneys were obtained at 1, 2, and 4 wk. Albuminuria was noted at 2 wk, but resolved after 4 wk. This was associated with glomerular IC deposits and mesangial proliferation. Glomerular macrophage infiltration was prominent at 1 and 2 wk, which resolved at 4 wk. Expression of monocyte chemoattractant protein-1 (MCP-1) and RANTES mRNA was upregulated at week 1 and decreased to control levels at weeks 2 and 4. The expression was localized to glomeruli by in situ hybridization and immunohistochemistry. The mRNA of CCR1, CCR2, and CCR5 but not CCR3 or CCR4 were upregulated at week 1 and decreased at weeks 2 and 4. Expression of CCR5 was located to the glomerulus by in situ hybridization and quantitative reverse transcription-PCR of isolated glomeruli. In summary, in a model of transient IC-GN, MCP-1 and RANTES and their receptors CCR1, CCR2, and CCR5 are expressed early and are already downregulated at the peak of proteinuria and leukocyte infiltration. Resolution of glomerulonephritis is associated with a return to baseline of chemokine and CCR expression. Therefore, it is concluded that glomerular MCP-1 and RANTES production directs circulating leukocytes that express CCR1, CCR2, and CCR5 into the glomerulus. After initiating GN, MCP-1 and RANTES and their receptors are readily downregulated.
authors.affiliation: Nephrological Center, Medical Policlinic, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Anders
authors.affiliation: Nephrological Center, Medical Policlinic, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Vielhauer
authors.affiliation: Nephrological Center, Medical Policlinic, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kretzler
authors.affiliation: Nephrological Center, Medical Policlinic, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Clemens D
authors.initials: CD
authors.lastname: Cohen
authors.affiliation: Nephrological Center, Medical Policlinic, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Segerer
authors.affiliation: Nephrological Center, Medical Policlinic, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Bruno
authors.initials: B
authors.lastname: Luckow
authors.affiliation: Nephrological Center, Medical Policlinic, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Weller
authors.affiliation: Division of Experimental Pathology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.affiliation: Nephrological Center, Medical Policlinic, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Schlöndorff
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000008:administration & dosage; D001483:Base Sequence; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005921:Glomerulonephritis / Q000209:etiology / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D007105:Immune Complex Diseases / Q000209:etiology / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007962:Leukocytes / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018925:Chemokines; D017931:DNA Primers; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D001052:Apoferritins