alpha d beta 2 integrin is expressed on human eosinophils and functions asan alternative ligand for vascular cell adhesion molecule 1 (VCAM-1)

The beta 2, family of integrins, CD11a, CD11b, CD11c, and alpha d,, are exp ressed on most leukocytes. We show that die newest member of this family, a lpha d, is expressed on human eosinophils in peripheral blood, and surface expression can be upregulated within minutes by phorbol ester or calcium io nophore 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 a lpha 4 integrin expression. Eosinophils isolated from late phase bronchoalv eolar 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 isolat ed and IL-5-cultured eosinophils, as well as alpha d beta 2-transfected Chi nese hamster ovary cells, alpha d beta 2 can function as a ligand for vascu lar cell adhesion molecule 1 (VCAM-1). This conclusion is based on the abil ity of monoclonal antibodies to alpha d, beta 2, or VCAM-1 to block cell at tachment in static adhesion assays. In experiments with eosinophils, the re lative contribution of alpha d beta 2 integrin-mediated adhesion is enhance d 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 eosi nophil adhesion to VCAM-1 in states of chronic inflammation.