RGD Reference Report - Blocking of monocyte chemoattractant protein-1 during tubulointerstitial nephritis resulted in delayed neutrophil clearance. - Rat Genome Database

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Blocking of monocyte chemoattractant protein-1 during tubulointerstitial nephritis resulted in delayed neutrophil clearance.

Authors: Li, P  Garcia, GE  Xia, Y  Wu, W  Gersch, C  Park, PW  Truong, L  Wilson, CB  Johnson, R  Feng, L 
Citation: Li P, etal., Am J Pathol. 2005 Sep;167(3):637-49.
RGD ID: 2303093
Pubmed: PMID:16127145   (View Abstract at PubMed)
PMCID: PMC1698738   (View Article at PubMed Central)
DOI: DOI:10.1016/S0002-9440(10)62039-1   (Journal Full-text)

The chemokine monocyte chemoattractant protein (MCP)-1 has been implicated in the monocyte/macrophage infiltration that occurs during tubulointerstitial nephritis (TIN). We investigated the role of MCP-1 in rats with TIN by administering a neutralizing anti-MCP-1 antibody (Ab). We observed significantly reduced macrophage infiltration and delayed neutrophil clearance in the kidneys of TIN model rats treated with the anti-MCP-1 Ab. To exclude the possibility that an observed immune complex could affect the resolution of apoptotic neutrophils via the Fc receptor, TIN model rats were treated with a peptide-based MCP-1 receptor antagonist (RA). The MCP-1 RA had effects similar to those of the anti-MCP-1 Ab. In addition, MCP-1 did not affect macrophage-mediated phagocytosis of neutrophils in vitro. Deposition of the anti-MCP-1 Ab in rat kidneys resulted from its binding to heparan sulfate-immobilized MCP-1, as demonstrated by the detection of MCP-1 in both pull-down and immunoprecipitation assays. We conclude that induction of chemokines, specifically MCP-1, in TIN corresponds with leukocyte infiltration and that the anti-MCP-1 Ab formed an immune complex with heparan sulfate-immobilized MCP-1 in the kidney. Antagonism of MCP-1 in TIN by Ab or RA may alter the pathological process, most likely through delayed removal of apoptotic neutrophils in the inflammatory loci.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
macrophage chemotaxis  IDA 2303093 RGD 
neutrophil chemotaxis  IMP 2303093 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
chemokine activity  IDA 2303093 RGD 
heparin binding  IPIheparin2303093 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl2  (C-C motif chemokine ligand 2)


Additional Information