THE CCR5 LIGANDS MIP‐1α AND RANTES MODULATE EOTAXIN‐3 (CCL26) SYNTHESIS AND RELEASE BY ALVEOLAR TYPE II CELLS

Alveolar type II cells are significant source of the eotaxins (CCL11, CCL24 and CCL26) which induce emigration and activation of eosinophils. We recently reported that these cells express CCR3 receptors and large quantities of CCL26 which auto‐regulate CCR3 receptors and other eotaxins. CCR5 ligands such as MIP‐1a and RANTES have been implicated in the pathogenesis of inflammatory conditions including asthma. To further understand airway epithelial cell chemokine receptor‐ligand pathway interactions, studies were designed to characterize CCR5 receptors in alveolar type II cells and investigate its role in modulation of eotaxins synthesis and secretion. Using A549 alveolar type II cells, we present data showing constitutive surface expression of CCR5 which is enhanced in the presence of MIP‐1a or RANTES. MIP‐1a also induced CCR5 mRNA and protein expression. Neither MIP‐1a nor RANTES induced constitutive or IL4 dependent release of CCL11, CCL24 or CCL26. However, MIP‐1a decreased synthesis of CCL26 and inhibited IL‐4 dependent CCL26 mRNA expression. Anti‐CCR5 or CCR5 antagonist met‐RANTES decreased IL‐4‐induced CCL26 synthesis and secretion respectively. These results suggest that CCR5 receptor ligand pathways modulate leukocytes chemoattraction factors involved in asthmatic inflammation. However, its regulatory pattern appears to oppose CCR3‐ligand pathway. (Supported by NIH MBRS/SCORE GM08111 and RCMI RR3320).