Interleukin-13 induces PSGL-1/P-selectin-dependent adhesion of eosinophils, but not neutrophils, to human umbilical vein endothelial cells under flow

Selective eosinophil accumulation is a hallmark of diseases such as asthma, In a model of chronic eosinophilic inflammation, we have previously shown that the tethering step in eosinophil adhesion is mediated by PSGL-1 bindin g to P-selectin. The Th2-associated cytokine IL-13 is of potential importan ce in allergic disease. We have therefore investigated whether IL-13 can me diate eosinophil binding to human umbilical vein endothelial cells (HUVEC) through P-selectin. IL-13 caused dose- and time-dependent increases of P-se lectin expression, as assessed by flow and laser scanning cytometry. A simi lar degree of expression was observed with IL-4, There was no effect on E-s electin or ICAM-1 expression. Tumor necrosis factor-alpha induced the expre ssion of VCAM-1, E-selectin, and ICAM-1 but had no effect on P-selectin exp ression, IL-13 increased the production of mRNA for surface and soluble var iants of P-selectin. Under flow conditions, eosinophils, but not neutrophil s, showed enhanced binding to IL-13 and to IL-4-stimulated HUVEC compared t o medium-cultured cells. Eosinophil adhesion was completely inhibited by a blocking monoclonal antibody against PSGL-1 and P-selectin. Anti-VLA-4 and anti-VCAM-1 antibodies inhibited binding to a lesser extent. Thus, at physi ologic levels of expression Induced by Th2 cytokines, P-selectin/PSGL-1 sup ported eosinophil but not neutrophil adhesion. This mechanism is likely to be a key event leading to the selective accumulation of eosinophils in alle rgic inflammation. (C) 2000 by The American Society of Hematology.