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

Eur J Immunol. 1998 Jan;28(1):80-9. 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 beta2 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 beta2 integrin-mediated adhesion was found to be augmented by E-zz without alteration in levels of surface expression of alphaMbeta2 or the "activation" reporter epitope defined by monoclonal antibody 24. Concomitantly with increased beta2 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD18 Antigens / physiology
  • Cell Adhesion
  • Chemotactic Factors / pharmacology
  • Chemotaxis, Leukocyte / drug effects
  • Disease Progression
  • E-Selectin / pharmacology*
  • Endothelium, Vascular / cytology
  • Humans
  • Intestinal Perforation / complications
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / drug effects*
  • Neutrophils / physiology
  • Reactive Oxygen Species / metabolism
  • Recombinant Proteins / pharmacology
  • Respiratory Burst
  • Respiratory Distress Syndrome / blood
  • Respiratory Distress Syndrome / etiology
  • Respiratory Distress Syndrome / pathology*
  • Risk
  • Solubility
  • Superoxides / metabolism


  • CD18 Antigens
  • Chemotactic Factors
  • E-Selectin
  • Reactive Oxygen Species
  • Recombinant Proteins
  • Superoxides
  • N-Formylmethionine Leucyl-Phenylalanine