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PMID: 16127145 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

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

The American journal of pathology ·Vol. 167 ·No. 3 ·2005-09-00 ·Pages 637-49

Li P, Garcia GE, Xia Y, Wu W, Gersch C, Park PW, Truong L, Wilson CB, Johnson R, Feng L

Abstract

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.

MeSH Terms
Animals Antibodies/immunology,pharmacology Antigen-Antibody Complex Apoptosis Chemokine CCL2/analogs & derivatives,antagonists & inhibitors,chemistry,immunology Chemokines Chemokines, CXC/metabolism Chemotaxis/drug effects Cytokines/metabolism Escherichia coli/metabolism Fibrosis Heparitin Sulfate/pharmacology Intercellular Signaling Peptides and Proteins/metabolism Kidney/immunology,metabolism Macrophages, Peritoneal Nephritis, Interstitial/metabolism,pathology,physiopathology Neutrophil Infiltration Neutrophils/drug effects,pathology Peptide Fragments/immunology,pharmacology Phagocytosis Rats Rats, Inbred BN Receptors, CCR2 Receptors, Chemokine/antagonists & inhibitors Time Factors
Chemicals
Antibodies Antigen-Antibody Complex Ccr2 protein, rat Chemokine CCL2 Chemokines Chemokines, CXC Cytokines Intercellular Signaling Peptides and Proteins Peptide Fragments Receptors, CCR2 Receptors, Chemokine keratinocyte-derived chemokines Heparitin Sulfate
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Li Ping
Department of Medicine, Renal and Infectious Disease Sections, Baylor College of Medicine, Houston, TX 77030. [email protected]
Garcia Gabriela E
Xia Yiyang
Wu Wei
Gersch Christine
Park Pyong Woo
Truong Luan
Wilson Curtis B
Johnson Richard
Feng Lili
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)62039-1
Email
[email protected]
Published
2005-09-00
Pages
637-49
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1698738
Subset
IM
Grants
NIDDK NIH HHS · 1P50-DK064233 · United States
NIDDK NIH HHS · R01-DK55730-02 · United States
NIDDK NIH HHS · P50 DK064233 · United States
NIDDK NIH HHS · R01 DK055730 · United States
NIDDK NIH HHS · R01-DK54674-02 · United States
NIDDK NIH HHS · R01 DK054674 · United States
BLRD VA · I01 BX002586 · United States
External Links
PubMed source DOI: 10.1016/S0002-9440(10)62039-1 PMC Full Text View journal details
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