Expression of CXCR4 in eosinophils: Functional analyses and cytokine-mediated regulation

We examined the expression of transcripts of a panel of chemokine receptors in human eosinophils and found intense constitutive expression of CXCR4 mR NA. Although surface CXCR4 protein was hardly detectable in the peripheral blood or freshly isolated eosinophils, surface expression of CXCR4 became g radually apparent during incubation at 37 degrees C. In contrast, the level of CCR3 expression was virtually unchanged during the incubation, Stromal cell-derived factor-1 alpha (SDF-1 alpha), the natural ligand of CXCR4, eli cited an apparent Ca2+ influx in these cells and induced a strong migratory response comparable to that by eotaxin, The surface expression of CXCR4 in eosinophils was up-regulated by IFN-gamma, TNF-LY, and TGF-beta while it w as down-regulated by IL-4 and eosinophil-directed hemopoietins such as IL-5 . The CXCR4 expression did not always parallel the apoptotic changes in cyt okine-treated eosinophils. In contrast to IL-4 and IFN-gamma, IL-5 potently reduced the level of CXCR4 mRNA, It seems unlikely that CXCR4 is fundament ally involved in the pathogenesis of allergic disorders by inducing the mig ration of eosinophils toward inflammatory sites, because a Th2-dominant sta te down-regulates eosinophil CXCR4 expression. However, CXCR4 may affect th e size of the mobilizable pool by holding eosinophils at noninflamed tissue s, Th2-dominant state may favor the liberation of eosinophils by down-regul ating CXCR4 expression, The interplay between CXCR4 and SDF-1 alpha in eosi nophils potentially plays an important role in the accumulation of these ce lls at the allergic inflammatory sites.