Potential pro‐inflammatory effects of soluble E‐selectin upon neutrophil function

• Published in: European journal of immunology 1998-01, Vol.28 (1), p.80-89
• Main Authors: Ruchaud‐Sparagano, Marie‐Hélène, Drost, Ellen M., Donnelly, Seamas C., Bird, Michael I., Haslett, Christopher, Dransfield, Ian
• Format: Article
• Language: English
• Subjects: Adhesion molecule; CD18 Antigens - physiology; Cell Adhesion; Chemotactic Factors - pharmacology; Chemotaxis, Leukocyte - drug effects; Disease Progression; E-Selectin - pharmacology; Endothelium, Vascular - cytology; E‐selectin; Humans; Inflammation; Intestinal Perforation - complications; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Neutrophil; Neutrophils - drug effects; Neutrophils - physiology; Reactive Oxygen Species - metabolism; Recombinant Proteins - pharmacology; Respiratory Burst; Respiratory Distress Syndrome, Adult - blood; Respiratory Distress Syndrome, Adult - etiology; Respiratory Distress Syndrome, Adult - pathology; Risk; Solubility; Superoxides - metabolism
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/(SICI)1521-4141(199801)28:01<80::AID-IMMU80>3.0.CO;2-7

Appropriate recruitment of neutrophils to sites of infection or tissue injury is a key event in the inflammatory response. A number of studies have shown the critical role of selectins in tethering and rolling of neutrophils on vascular endothelium, as well as a more complex regulatory role, since they have the potential to alter leukocyte recruitment by triggering β2 integrin‐mediated adhesion. In this study, we 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 neutrophil granulocytes are implicated in ARDS pathogenesis, we have investigated the possibility of a link between elevated soluble plasma E‐selectin levels and disease progression by examining the effects of soluble recombinant E‐selectin (E‐zz) upon neutrophil function. In this paper, we describe the novel finding that exposure of neutrophils to E‐zz potentiates a number of neutrophil functions which may act to drive inflammatory processes. Although neutrophil deformability, an important parameter determining retention within the lung microvasculature, was not affected by E‐zz, neutrophil polarization was observed. In addition, neutrophil β2 integrin‐mediated adhesion was found to be augmented by E‐zz without alteration in levels of surface expression of αMβ2 or the “activation” reporter epitope defined by monoclonal antibody 24. Concomitantly with increased β2 integrin‐mediated adhesion, we observed an inhibition of formyl‐Met‐Leu‐Phe‐directed chemotaxis. Together with an augmentation of neutrophil reactive oxidant species production and release of superoxide anions, these data raise the possibility that soluble E‐selectin exerts pro‐inflammatory effects upon neutrophil function at sites of inflammation, thereby exacerbating disease processes.