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

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 d beta 2 ligands, in both freshly isolated and IL-5-cultured eosinophils, as well as alpha d beta 2-transfected Chinese hamster ovary cells, alpha d beta 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 ad, beta 2, or VCAM-1 to block cell attachment in static adhesion assays. In experiments with eosinophils, the relative contribution of alpha d beta 2 integrin-mediated adhesion is enhanced after IL-5 culture. These experiments demonstrate that alpha d beta 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.