POTENTIAL PRO-INFLAMMATORY EFFECTS OF SOLUBLE E-SELECTIN UPON NEUTROPHIL FUNCTION

Appropriate recruitment of neutrophils to sites of infection or tissue injury is a key event in the inflammatory response. A number of studi es have shown the critical role of selectins in tethering and rolling of neutrophils on vascular endothelium, as well as a more complex regu latory role, since they have the potential to alter leukocyte recruitm ent by triggering beta(2) integrin-mediated adhesion. In this study, w e report that in contrast to patients ''at risk'' of developing acute respiratory disease syndrome (ARDS), elevated plasma levels of soluble E-selectin are found in patients with established disease. Since neut rophil granulocytes are implicated in ARDS pathogenesis, we have inves tigated the possibility of a link between elevated soluble plasma E-se lectin levels and disease progression by examining the effects of solu ble recombinant E-selectin (E-zz) upon neutrophil function. In this pa per, we describe the novel finding that exposure of neutrophils to E-z z potentiates a number of neutrophil functions which may act to drive inflammatory processes. Although neutrophil deformability, an importan t parameter determining retention within the lung microvasculature, wa s not affected by E-zz, neutrophil polarization was observed. In addit ion, neutrophil beta(2) integrin-mediated adhesion was found to be aug mented by E-zz without alteration in levels of surface expression of a lpha(M) beta(2) or the ''activation'' reporter epitope defined by mono clonal antibody 24. Concomitantly with increased beta(2) integrin-medi ated adhesion, we observed an inhibition of formyl-Met-Leu-Phe-directe d chemotaxis. Together with an augmentation of neutrophil reactive oxi dant species production and release of superoxide anions, these data r aise the possibility that soluble E-selectin exerts pro-inflammatory e ffects upon neutrophil function at sites of inflammation, thereby exac erbating disease processes.