PMID- 11316850 OWN - NLM STAT- MEDLINE DCOM- 20010809 LR - 20210511 IS - 1046-6673 (Print) IS - 1046-6673 (Linking) VI - 12 IP - 5 DP - 2001 May TI - Chemokine and chemokine receptor expression during initiation and resolution of immune complex glomerulonephritis. PG - 919-931 LID - 10.1681/ASN.V125919 [doi] AB - 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. FAU - Anders, Hans-Joachim AU - Anders HJ AD - Nephrological Center, Medical Policlinic, Ludwig-Maximilians-University Munich, Munich, Germany. FAU - Vielhauer, Volker AU - Vielhauer V AD - Nephrological Center, Medical Policlinic, Ludwig-Maximilians-University Munich, Munich, Germany. FAU - Kretzler, Matthias AU - Kretzler M AD - Nephrological Center, Medical Policlinic, Ludwig-Maximilians-University Munich, Munich, Germany. FAU - Cohen, Clemens D AU - Cohen CD AD - Nephrological Center, Medical Policlinic, Ludwig-Maximilians-University Munich, Munich, Germany. FAU - Segerer, Stephan AU - Segerer S AD - Nephrological Center, Medical Policlinic, Ludwig-Maximilians-University Munich, Munich, Germany. FAU - Luckow, Bruno AU - Luckow B AD - Nephrological Center, Medical Policlinic, Ludwig-Maximilians-University Munich, Munich, Germany. FAU - Weller, Lars AU - Weller L AD - Nephrological Center, Medical Policlinic, Ludwig-Maximilians-University Munich, Munich, Germany. FAU - Grone, Hermann-Josef AU - Grone HJ AD - Division of Experimental Pathology, German Cancer Research Center, Heidelberg, Germany. FAU - Schlondorff, Detlef AU - Schlondorff D AD - Nephrological Center, Medical Policlinic, Ludwig-Maximilians-University Munich, Munich, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Am Soc Nephrol JT - Journal of the American Society of Nephrology : JASN JID - 9013836 RN - 0 (Chemokines) RN - 0 (DNA Primers) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Chemokine) RN - 9013-31-4 (Apoferritins) SB - IM MH - Animals MH - Apoferritins/administration & dosage MH - Base Sequence MH - Chemokines/*genetics/*metabolism MH - DNA Primers/genetics MH - Female MH - Gene Expression MH - Glomerulonephritis/etiology/*genetics/*immunology/pathology MH - Immune Complex Diseases/etiology/*genetics/*immunology/pathology MH - Immunohistochemistry MH - In Situ Hybridization MH - Leukocytes/pathology MH - Mice MH - Mice, Inbred BALB C MH - Microscopy, Electron MH - RNA, Messenger/genetics/metabolism MH - Receptors, Chemokine/*genetics/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2001/04/24 10:00 MHDA- 2001/08/10 10:01 CRDT- 2001/04/24 10:00 PHST- 2001/04/24 10:00 [pubmed] PHST- 2001/08/10 10:01 [medline] PHST- 2001/04/24 10:00 [entrez] AID - 12/5/919 [pii] AID - 10.1681/ASN.V125919 [doi] PST - ppublish SO - J Am Soc Nephrol. 2001 May;12(5):919-931. doi: 10.1681/ASN.V125919.