RGD Reference Report - Chemokine receptor expression in rat adjuvant-induced arthritis. - Rat Genome Database

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Chemokine receptor expression in rat adjuvant-induced arthritis.

Authors: Haas, CS  Martinez, RJ  Attia, N  Haines GK, 3RD  Campbell, PL  Koch, AE 
Citation: Haas CS, etal., Arthritis Rheum. 2005 Dec;52(12):3718-30.
RGD ID: 4144893
Pubmed: PMID:16320322   (View Abstract at PubMed)
DOI: DOI:10.1002/art.21476   (Journal Full-text)

OBJECTIVE: Chemokine receptors mediate leukocyte migration into inflamed rheumatoid arthritis (RA) synovial tissue (ST). Knowledge of their distribution is crucial for understanding the evolution of the inflammatory process. In this study, we used rat adjuvant-induced arthritis (AIA), a model for RA, to define the temporospatial expression of chemokine receptors. METHODS: ST from rats with AIA was immunostained, the percentage of cells expressing each receptor was determined, and findings were correlated with levels of inflammation. Chemokine receptor expression was evaluated on rat macrophages in vitro. RESULTS: CCR1, a receptor for macrophage inflammatory protein 1alpha (MIP-1alpha)/CCL3 and RANTES/CCL5, exhibited high constitutive expression on macrophages in AIA. CCR5, binding MIP-1alpha/CCL3 and RANTES/CCL5, was up-regulated on ST macrophages during the course of AIA, correlating with macrophage expression of CCR2, a receptor for monocyte chemoattractant protein 1/CCL2. Endothelial cell (EC) CCR2 was down-regulated as arthritis progressed, inversely correlating with inflammation. CCR3, another RANTES/CCL5 receptor, was constitutively high on macrophages in vivo and in vitro, with down-regulation during AIA. CXCR4, a receptor for stromal cell-derived factor 1/CXCL12), was prominently up-regulated on ECs, preceding the peak of inflammation. CONCLUSION: These findings show that 1) constitutive expression of CCR1 on macrophages remains high during AIA; 2) CCR2 and CCR3 may play a role in initial recruitment of leukocytes to ST in AIA; 3) macrophage expression of CCR2 and CCR5 may be important for sustaining inflammatory changes; and 4) EC CXCR4 may be a harbinger of inflammatory changes. Our results may help guide chemokine receptor blockade-targeting treatment strategies in inflammatory arthritis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Arthritis  ISOCcr2 (Rattus norvegicus)4144893; 4144893 RGD 
Experimental Arthritis  IEP 4144893 RGD 
Inflammation  ISOCcr5 (Rattus norvegicus)4144893; 4144893associated with Arthritis more ...RGD 
Inflammation  IEP 4144893associated with Arthritis more ...RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cell surface  IDA 4144893 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccr2  (C-C motif chemokine receptor 2)
Ccr5  (C-C motif chemokine receptor 5)

Genes (Mus musculus)
Ccr2  (C-C motif chemokine receptor 2)
Ccr5  (C-C motif chemokine receptor 5)

Genes (Homo sapiens)
CCR2  (C-C motif chemokine receptor 2)
CCR5  (C-C motif chemokine receptor 5)


Additional Information