Expression and function of ß1 integrins on human eosinophils

RESUMO

Eosinophils preferentially accumulate at sites of chronic allergic diseases such as bronchial asthma. Tha mechanisms by which selective eosinophil migration occurs are not fully understood. However, interactions of cell-surface adhesion molecules on the eosinophil with molecular counterligands on endothelial and epithelial cells, and on extracellular matrix proteins, are likely to be critical during the recruitment process. One possible mechanism for selective eosinophil recruitment involves the alpha4ß1 (VLA-4) integrin which is not expressed on eosinophils. Correlations have been found between infiltration of eosinophils and endothelial expression of VCAM-1, the ligand for VLA-4, in the lungs of asthmatic individuals as well as in late rections in the lungs, nose and skin. Epithelial and endothelial cells respond to the Th2-type cytokines IL-4 and IL-13 with selective de novo expression of VCAM-1, consistent with the possible role of VCAM-1/VLA-4 interactions in eosinophil influx during allergic inflammation. Both ß1 and ß2 integrins on eosinophils exist in a state of partial activation. For example, eosinophils can be maximally activated for adhesion to VCAM-1 or fibronectin after exposure to ß1 integrin-activating antibodies or divalent cations, conditions that do not necessarily affect the total cell surface expression of ß1 integrins. In contrast, cytokines like IL-5 prevent ß1 integrin activation while promoting ß2 integrin function. Furthermore, ligation of integrins can regulate the affector functions of the cell. For example, eosinophil adhesion via ß1 and/or ß2 integrins has been shown to alter a variety of functional responses including degranulation and apoptosis. Thus, integrins appear to be important in mediating eosinophil migration and activation in allergic inflammation. Strategies that interfere with these processes may prove to be useful for treatment of allergic diseases.