Retinoic acids up‐regulate functional eosinophil‐driving receptor CCR 3

Eotaxins and their receptor CCR 3 have a definitive role for tissue accumulation of eosinophils both under homeostatic and pathologic conditions. However, physiological stimuli that can up‐regulate CCR 3 in blood‐derived human eosinophils have not been recognized. As a prior gene microarray study revealed up‐regulation of CCR 3 in eosinophils stimulated with retinoic acids ( RA s), the expression of functional CCR 3 was examined. We found that 9‐cis RA and all‐trans RA ( ATRA ) significantly induced surface CCR 3 expression regardless of the presence of IL ‐3 or IL ‐5. Pharmacological manipulations with receptor‐specific agonists and antagonists indicated that retinoic acid receptor‐α activation is critical for CCR 3 up‐regulation. RA ‐induced CCR 3 was associated with its functional capacity, in terms of the calcium mobilization and chemotactic response to eotaxin‐1 ( CCL 11). Our study suggests an important role of vitamin A derivatives in the tissue accumulation of eosinophils.