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Article: Monocyte chemoattractant protein-1 promotes macrophage-mediated tubular injury, but not glomerular injury, in nephrotoxic serum nephritis

TitleMonocyte chemoattractant protein-1 promotes macrophage-mediated tubular injury, but not glomerular injury, in nephrotoxic serum nephritis
Authors
Issue Date1999
PublisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.org
Citation
Journal of Clinical Investigation, 1999, v. 103 n. 1, p. 73-80 How to Cite?
AbstractMonocyte chemoattractant protein-1 (MCP-1) is upregulated in renal parenchymal cells during kidney disease. To investigate whether MCP-1 promotes tubular and/or glomerular injury, we induced nephrotoxic serum nephritis (NSN) in MCP-1 genetically deficient mice. Mice were analyzed when tubules and glomeruli were severely damaged in the MCP-1–intact strain (day 7). MCP-1 transcripts increased fivefold in MCP-1–intact mice. MCP-1 was predominantly localized within cortical tubules (90%), and most cortical tubules were damaged, whereas few glomerular cells expressed MCP-1 (10%). By comparison, there was a marked reduction (>40%) in tubular injury in MCP-1–deficient mice (histopathology, apoptosis). MCP-1–deficient mice were not protected from glomerular injury (histopathology, proteinuria, macrophage influx). Macrophage accumulation increased adjacent to tubules in MCP-1–intact mice compared with MCP-1–deficient mice (70%, P < 0.005), indicating that macrophages recruited by MCP-1 induce tubular epithelial cell (TEC) damage. Lipopolysaccharide-activated bone marrow macrophages released molecules that induced TEC death that was not dependent on MCP-1 expression by macrophages or TEC. In conclusion, MCP-1 is predominantly expressed by TEC and not glomeruli, promotes TEC and not glomerular damage, and increases activated macrophages adjacent to TEC that damage TEC during NSN. Therefore, we suggest that blockage of TEC MCP-1 expression is a therapeutic strategy for some forms of kidney disease.
Persistent Identifierhttp://hdl.handle.net/10722/42143
ISSN
2015 Impact Factor: 12.575
2015 SCImago Journal Rankings: 8.764
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorTesch, GHen_HK
dc.contributor.authorSchwarting, Aen_HK
dc.contributor.authorKinoshita, Ken_HK
dc.contributor.authorLan, HYen_HK
dc.contributor.authorRollins, BJen_HK
dc.contributor.authorKelley, VRen_HK
dc.date.accessioned2007-01-08T02:30:11Z-
dc.date.available2007-01-08T02:30:11Z-
dc.date.issued1999en_HK
dc.identifier.citationJournal of Clinical Investigation, 1999, v. 103 n. 1, p. 73-80en_HK
dc.identifier.issn0021-9738en_HK
dc.identifier.urihttp://hdl.handle.net/10722/42143-
dc.description.abstractMonocyte chemoattractant protein-1 (MCP-1) is upregulated in renal parenchymal cells during kidney disease. To investigate whether MCP-1 promotes tubular and/or glomerular injury, we induced nephrotoxic serum nephritis (NSN) in MCP-1 genetically deficient mice. Mice were analyzed when tubules and glomeruli were severely damaged in the MCP-1–intact strain (day 7). MCP-1 transcripts increased fivefold in MCP-1–intact mice. MCP-1 was predominantly localized within cortical tubules (90%), and most cortical tubules were damaged, whereas few glomerular cells expressed MCP-1 (10%). By comparison, there was a marked reduction (>40%) in tubular injury in MCP-1–deficient mice (histopathology, apoptosis). MCP-1–deficient mice were not protected from glomerular injury (histopathology, proteinuria, macrophage influx). Macrophage accumulation increased adjacent to tubules in MCP-1–intact mice compared with MCP-1–deficient mice (70%, P < 0.005), indicating that macrophages recruited by MCP-1 induce tubular epithelial cell (TEC) damage. Lipopolysaccharide-activated bone marrow macrophages released molecules that induced TEC death that was not dependent on MCP-1 expression by macrophages or TEC. In conclusion, MCP-1 is predominantly expressed by TEC and not glomeruli, promotes TEC and not glomerular damage, and increases activated macrophages adjacent to TEC that damage TEC during NSN. Therefore, we suggest that blockage of TEC MCP-1 expression is a therapeutic strategy for some forms of kidney disease.en_HK
dc.format.extent388029 bytes-
dc.format.extent284160 bytes-
dc.format.mimetypeapplication/pdf-
dc.format.mimetypeapplication/msword-
dc.languageengen_HK
dc.publisherAmerican Society for Clinical Investigation. The Journal's web site is located at http://www.jci.orgen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshDisease models, animalen_HK
dc.subject.meshKidney glomerulus - metabolismen_HK
dc.subject.meshMacrophages - metabolismen_HK
dc.subject.meshMice, knockouten_HK
dc.subject.meshKidney glomerulusen_HK
dc.titleMonocyte chemoattractant protein-1 promotes macrophage-mediated tubular injury, but not glomerular injury, in nephrotoxic serum nephritisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9738&volume=103&issue=1&spage=73&epage=80&date=1999&atitle=Monocyte+chemoattractant+protein-1+promotes+macrophage-mediated+tubular+injury,+but+not+glomerular+injury,+in+nephrotoxic+serum+nephritisen_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.pmid9884336-
dc.identifier.pmcidPMC407867-
dc.identifier.scopuseid_2-s2.0-0032919614-
dc.identifier.hkuros47116-
dc.identifier.isiWOS:000077948100011-

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