Invited Symposium: Novel Cellular and Molecular Mechanisms in Allergic Inflammation
van der Vieren, M (ICOS Corporation, Bothell, USA)
Gallatin, WM (ICOS Corporation, Bothell, WA, USA)
Hoffman, PA (ICOS Corporation, Bothell, WA, USA)
Staunton, D (ICOS Corporation, Bothell, WA, USA)
Bochner, BS (Johns Hopkins Asthma and Allergy Center, Baltimore, USA)
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 IL-5 leads to a 2-4 fold increase in alpha d levels by 3-7 days 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 days 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 CHO cells, alpha d/beta 2 can function as a ligand for VCAM-1. This conclusion is based on the ability of mAbs 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 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.
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|Grayson, MH; van der Vieren, M; Gallatin, WM; Hoffman, PA; Staunton, D; Bochner, BS; (1998). Alpha d/beta 2 Integrin Is a Ligand For Vascular Cell Adhesion Molecule-1 (VCAM-1). Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/denburg/grayson0218/index.html|
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