Superoxide activates very late antigen-4 on an eosinophil cell line and increases cellular binding to vascular cell adhesion molecule-1

Abstract

The recruitment of eosinophils to the airway is a key event in the pathogenesis of allergy. Very late antigen-4 (VLA-4), an integrin ligand for vascular cell adhesion molecule-1 (VCAM-1), is expressed on eosinophils. VLA-4-mediated adhesion of eosinophils to VCAM-1 may contribute to their selective recruitment to tissues in allergy. Reactive oxygen species (ROS), including nitric oxide (NO), are abundant in the airway of allergic patients, but their role in pathogenesis of allergy is unclear. In this investigation, we studied the effects of ROS on integrin-mediated eosinophil adhesion. Recombinant soluble VCAM-1 and ICAM-1 were used to test the effects of ROS on the integrin-mediated adhesion of an eosinophil cell line. We used phorbol 12-myristate 13-acetate-stimulated neutrophils and hypoxanthine to generate superoxide, NO donors as sources of NO, and a static cell-to-protein adhesion assay to analyze cellular adhesion. Stimulated neutrophils significantly increased eosinophil binding to VCAM-1, which was reversed in the presence of superoxide dismutase. Neutrophils from a chronic granulomatous disease patient lacked this activity in enhancing eosinophil adhesion. Our results suggest that the balance between ROS molecules in different tissue microenvironments may change the integrin-mediated leukocyte adhesion and is likely to be a key factor in leukocyte recruitment in allergic inflammation.