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The Journal of Immunology, 2001, 166: 588-595.
Copyright © 2001 by The American Association of Immunologists

IL-8 Induces a Transient Arrest of Rolling Eosinophils on Human Endothelial Cells1

Laurien H. Ulfman, Dianne P. H. Joosten, Jan A. M. van der Linden, Jan-Willem J. Lammers, Jaap Jan Zwaginga and Leo Koenderman2

Department of Pulmonary Diseases and Haematology, University Medical Center, Utrecht, The Netherlands

Eosinophils exhibit a rolling interaction with E-selectin-expressing endothelium, and need to be activated by inflammatory mediators to firmly adhere to this surface. This study shows that IL-8 induces a transient arrest of unprimed eosinophils that roll on E-selectin present on TNF-{alpha}-activated HUVEC in an in vitro flow chamber. This process was antagonized by neutralizing Abs directed against IL-8 showing the specificity of the IL-8 effect. Furthermore, blocking Abs against both {alpha}4 and {beta}2 integrins inhibited the IL-8-induced transient arrest while these Abs had no effect when they were added separately. The IL-8-induced arrest was pertussis toxin sensitive. Studying the effect of IL-8 in more detail, we evaluated putative changes in intracellular Ca2+ concentration in eosinophils induced by IL-8. We could show that IL-8 induces a transient rise in intracellular Ca2+ concentration in ~40% of the cells provided that the eosinophils are interacting with endothelial cells or fibronectin-coated surfaces. Together these data show that resting eosinophils respond to IL-8 provided that the cells adhere on physiological surfaces. The induction of a transient arrest provides a new level of chemokine-induced regulation of leukocyte adhesion under flow conditions.




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