Differential expression of chemokine receptors on peripheral blood, synovial fluid, and synovial tissue monocytes/macrophages in rheumatoid arthritis

Objective. Since it is likely that monocytes utilize chemokines to migrate to the rheumatoid arthritis (RA) joint, we investigated the expression of C -C chemokine receptors (CCR) 1-6 and C-X-C receptor 3 (CXCR3) in the periph eral blood (PB), synovial fluid (SF), and synovial tissue of patients with RA as well as in the PB of normal subjects. Methods. We compared chemokine receptor expression on CD14+ monocytes from normal PB, RA PB, and RA SF using 2-color flow cytometry. Correlations with patient clinical data were determined. Chemokine and receptor expression w ere investigated in RA synovial tissue by immunohistochemistry and 2-color immunofluorescence to identify CD68+ macrophages. Results. Most normal PB monocytes expressed CCR1 (87%) and CCR2 (84%), but not CCRs 3, 4, 5, or 6 or CXCR3. RA PB monocytes expressed CCR1 (56%) and C CR2 (76%), with significantly more expressing CCR3 (18%), CCR4 (38%), and C CR5 (17%) compared with normal PB monocytes. Significantly fewer SF monocyt es from RA patients expressed CCR1 (17%), CCR2 (24%), and CCR4 (6%) while s ignificantly more expressed CCR3 (35%) and CCR5 (47%) compared with RA and normal PB monocytes; CCR6 and CXCR3 were rarely detected. Clinically, the e rythrocyte sedimentation rate was inversely correlated with the expression of CCR1 and CCR4 by RA PB, and CCR5 expression by RA SF was correlated with the SF white blood cell count. CCR1-, CCR2-, and CCR5-immunoreactive cells were found in RA synovial tissue and colocalized with CD68+ macrophages. R A synovial tissue RANTES (regulated upon activation, normally T cell expres sed and secreted chemokine)- and monocyte chemoattractant protein 1-immunor eactive cells colocalized with CCR1 and CCR2, respectively, on serial secti ons. Macrophage inflammatory protein 1 alpha (MIP-1 alpha) was principally restricted to vascular endothelium, and MIP-1 beta+ macrophages were found throughout the sections. Conclusion. Monocytes mainly express CCR1 and CCR2 in normal and RA PB, CCR 3 and CCR5 in RA PB and RA SF, and CCR4 in RA PB. The differential expressi on of chemokine receptors suggests that certain receptors aid in monocyte r ecruitment from the circulation while others are important in monocyte rete ntion in the joint.