Phorbol Esters Alter α4 and αd Integrin Usage During Eosinophil Adhesion to VCAM-1

摘要

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 bothα4 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.