Chemokine receptor expression profile of eosinophils at inflamed tissue sites: Decreased CCR3 and increased CXCR4 expression by lung eosinophils

Background: To date, most studies dealing with eosinophil chemokine recepto rs have used eosinophils isolated from peripheral blood. During the movemen t of eosinophils from the peripheral blood to inflamed tissue sites, microe nvironmental signals might alter their expression of chemokine receptors, H owever, little is known about the profile of expression of chemokine recept ors by eosinophils at inflame tissue sites in human beings. Objective: The purpose of this study was to determine whether eosinophils t hat have migrated into inflamed tissues exhibit expression that is qualitat ively profile of chemokine receptor ex and/or quantitatively different from that of eosinophils in peripheral locations. Methods: We studied simultaneously the expression and function of chemokine receptors in eosinophils in both bronchoalveolar lavage fluid (BALF) and p eripheral blood specimens of 7 patients with eosinophilic lung diseases. Results: De novo expression of CCR2, CCR4, and CCR5 was not detected at eit her the protein or the mRNA level. However, surface expression of CCR3 was decreased and CXCR4 was conversely increased with statistical significance in BALF eosinophils. Moreover, the changes in CCR3 and CXCR4 expression wer e reflected in the altered migratory response to their ligands. On the othe r hand, the levels of CXCR1, CXCR2, CXCR3, and CCR1 were virtually unchange d in BALF eosinophils, and these receptors did not have functional signific ance. Conclusion: Eosinophils at inflamed tissue sites exhibited an expression pr ofile qualitatively similar to that in peripheral locations, except for dec reased CCR3 and increased CXCR4 expression. Our results suggest that CCR3 i s primarily and CXCR4 is cooperatively involved in eosinophil accumulation at inflamed tissue sites.