PMID- 9884336
OWN - NLM
STAT- MEDLINE
DCOM- 19990216
LR  - 20240411
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 103
IP  - 1
DP  - 1999 Jan
TI  - Monocyte chemoattractant protein-1 promotes macrophage-mediated tubular injury, 
      but not glomerular injury, in nephrotoxic serum nephritis.
PG  - 73-80
AB  - Monocyte 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.
FAU - Tesch, G H
AU  - Tesch GH
AD  - Laboratory of Molecular Autoimmune Disease, Renal Division, Brigham and Women's 
      Hospital, Boston, Massachusetts 02115, USA.
FAU - Schwarting, A
AU  - Schwarting A
FAU - Kinoshita, K
AU  - Kinoshita K
FAU - Lan, H Y
AU  - Lan HY
FAU - Rollins, B J
AU  - Rollins BJ
FAU - Kelley, V R
AU  - Kelley VR
LA  - eng
GR  - R01 DK036149/DK/NIDDK NIH HHS/United States
GR  - Z01 DK036149/ImNIH/Intramural NIH HHS/United States
GR  - DK 36149/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/*genetics/metabolism
MH  - Disease Models, Animal
MH  - Histocytochemistry
MH  - In Situ Nick-End Labeling
MH  - Kidney Glomerulus/*metabolism
MH  - Kidney Tubules/*pathology
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Nephritis/immunology/*pathology
MH  - Proteinuria
MH  - RNA, Messenger/analysis
MH  - T-Lymphocytes/metabolism
PMC - PMC407867
EDAT- 1999/01/12 00:00
MHDA- 1999/01/12 00:01
PMCR- 1999/01/01
CRDT- 1999/01/12 00:00
PHST- 1999/01/12 00:00 [pubmed]
PHST- 1999/01/12 00:01 [medline]
PHST- 1999/01/12 00:00 [entrez]
PHST- 1999/01/01 00:00 [pmc-release]
AID - 04876 [pii]
AID - 10.1172/JCI4876 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 Jan;103(1):73-80. doi: 10.1172/JCI4876.