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 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.
Ruchaud-Sparagano
M H
MH
Respiratory Medicine Unit, University of Edinburgh Medical School, GB.
Drost
E M
EM
Donnelly
S C
SC
Bird
M I
MI
Haslett
C
C
Dransfield
I
I
D018821:CD18 Antigens / Q000502:physiology; D002448:Cell Adhesion; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D018450:Disease Progression; D019040:E-Selectin / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007416:Intestinal Perforation / Q000150:complications; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D016897:Respiratory Burst; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000209:etiology / Q000473:pathology*; D012306:Risk; D012995:Solubility; D013481:Superoxides / Q000378:metabolism
D018821:CD18 Antigens; D002630:Chemotactic Factors; D019040:E-Selectin; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine