title: Phorbol esters alter alpha4 and alphad integrin usage during eosinophil adhesion to VCAM-1.
abstract: 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 alpha4 and alphad integrins under static and flow conditions. PMA increased surface expression of alphad integrins and decreased alpha4 integrin expression. Under static conditions, eosinophils bound well to VCAM-1, primarily via alpha4beta1 integrins, with a minor alphadbeta2 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 beta1 and beta2 integrins. Under flow conditions, eosinophils readily attached to VCAM-1, and adhesion was inhibited by both alpha4 and alphad mAbs (95 and 50% inhibition, respectively). Many fewer PMA-stimulated eosinophils bound to VCAM-1 under flow conditions, but both alpha4 and alphad mAbs inhibited adhesion equally. Thus, PMA alters eosinophil integrin expression and the relative contributions of alpha4 and alphad integrins during attachment to VCAM-1.
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
authors.forename: Matsuo
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tachimoto
authors.forename: Esra
authors.initials: E
authors.lastname: Nutku
authors.forename: Sherry A
authors.initials: SA
authors.lastname: Hudson
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Bochner
mesh_terms: D002273:Carcinogens / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D039001:Integrin alpha Chains; D019010:Vascular Cell Adhesion Molecule-1; D013755:Tetradecanoylphorbol Acetate