Chemokine receptor expression in rat adjuvant-induced arthritis.

Abstract

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.

• Authors: Christian S Haas, Rita J Martinez, Naweah Attia, G Kenneth Haines 3rd, Phillip L Campbell, Alisa E Koch
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 52 Issue 12 Pg. 3718-30 (Dec 2005) ISSN: 0004-3591 [Print] United States
• PMID: 16320322 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Ccr1 protein, rat
• Ccr2 protein, rat
• Ccr3 protein, rat
• Cxcr4 protein, rat
• Receptors, CCR1
• Receptors, CCR2
• Receptors, CCR3
• Receptors, CCR5
• Receptors, CXCR4
• Receptors, Chemokine

Topics

• Animals
• Arthritis, Experimental (immunology, metabolism)
• Cell Line
• Female
• Macrophages, Alveolar (cytology, immunology, metabolism)
• Myocytes, Smooth Muscle (immunology, metabolism)
• Rats
• Rats, Inbred Lew
• Receptors, CCR1
• Receptors, CCR2
• Receptors, CCR3
• Receptors, CCR5 (metabolism)
• Receptors, CXCR4 (metabolism)
• Receptors, Chemokine (metabolism)
• Synovial Membrane (immunology, metabolism)
• Up-Regulation