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Phorbol esters alter α4 and αd integrin usage during eosinophil adhesion to VCAM-1

We examined the effect of the protein kinase C activator phorbol-12-myristate-13-acetate (PMA) on the human eosinophil adhesion molecule phenotype and attachment to VCAM-1 via α4 and αd integrins under static and flow conditions. PMA increased surface expression of αd integrins and decreased α4 integrin expression. Under static conditions, eosinophils bound well to VCAM-1, primarily via α4β1 integrins, with a minor αdβ2 integrin component. Unexpectedly, PMA-stimulated eosinophils bound equally well to VCAM-1 and albumin in a temperature- and divalent cation-dependent manner, yet adhesion was independent of β1 and β2 integrins. Under flow conditions, eosinophils readily attached to VCAM-1, and adhesion was inhibited by both α4 and αd mAbs (95 and 50% inhibition, respectively). Many fewer PMA-stimulated eosinophils bound to VCAM-1 under flow conditions, but both α4 and αd mAbs inhibited adhesion equally. Thus, PMA alters eosinophil integrin expression and the relative contributions of α4 and αd integrins during attachment to VCAM-1.