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J. Exp. Med., Volume 188, Number 11, December 7, 1998 2187-2191

alpha dbeta 2 Integrin Is Expressed on Human Eosinophils and Functions as an Alternative Ligand for Vascular Cell Adhesion Molecule 1 (VCAM-1)

By Mitchell H. Grayson,* Monica Van der Vieren,Dagger Sherry A. Sterbinsky,* W. Michael Gallatin,Dagger Patricia A. Hoffman,Dagger Donald E. Staunton,Dagger and Bruce S. Bochner*

From * The Johns Hopkins University School of Medicine, Division of Clinical Immunology, Baltimore, Maryland 21224; and Dagger  ICOS Corporation, Bothell, Washington 98021

The beta 2 family of integrins, CD11a, CD11b, CD11c, and alpha d, are expressed on most leukocytes. We show that the newest member of this family, alpha d, is expressed on human eosinophils in peripheral blood, and surface expression can be upregulated within minutes by phorbol ester or calcium ionophore A23187. Culture of eosinophils with interleukin 5 (IL-5) leads to a two- to fourfold increase in alpha d levels by 3-7 d without a change in alpha 4 integrin expression. Eosinophils isolated from late phase bronchoalveolar lavage fluids express alpha d at levels similar to that seen after 3 d of IL-5 culture. Regarding alpha dbeta 2 ligands, in both freshly isolated and IL-5-cultured eosinophils, as well as alpha dbeta 2-transfected Chinese hamster ovary cells, alpha dbeta 2 can function as a ligand for vascular cell adhesion molecule 1 (VCAM-1). This conclusion is based on the ability of monoclonal antibodies to alpha d, beta 2, or VCAM-1 to block cell attachment in static adhesion assays. In experiments with eosinophils, the relative contribution of alpha dbeta 2 integrin- mediated adhesion is enhanced after IL-5 culture. These experiments demonstrate that alpha dbeta 2 is an alternative ligand for VCAM-1, and this integrin may play a role in eosinophil adhesion to VCAM-1 in states of chronic inflammation.

Key words: beta 2 integrineosinophiladhesionvascular cell adhesion molecule 1


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