Increased serum soluble Fas after major XXXX is associated with delayed neutrophil apoptosis and development of @entity295 .

@entity1 @entity650 @entity295 @entity11891 @entity2667 @entity881 @entity130
INTRODUCTION: Deregulated apoptosis and overshooting neutrophil functions contribute to immune and organ dysfunction in @entity295 and @entity881 ( @entity881 ). In the present study, we determined the role of soluble Fas (sFas) in the regulation of posttraumatic neutrophil extrinsic apoptosis and the development of @entity295 . METHODS: Forty-seven major @entity130 @entity1 , 18 with and 29 without @entity295 development during the first 10 days after @entity130 , were enrolled in this prospective study. Seventeen healthy volunteers served as controls. Blood samples from severely injured @entity1 were analyzed at day 1, day 5 and day 9 after major @entity130 . sFas levels, plasma levels of neutrophil elastase ( @entity11891 ) and levels of @entity650 were quantified by enzyme-linked immunosorbent assay and related to @entity1 ' Sequential Organ Failure Assessment (SOFA) score and Multiple Organ Dysfunction Score (MODS). Neutrophil apoptosis was determined by @entity2667 staining of fragmented DNA and flow cytometry. sFas-mediated effects on neutrophil apoptosis were investigated in cells cultured with agonistic anti-Fas antibodies in the presence of recombinant sFas, sFas-depleted serum or untreated serum from septic patients. RESULTS: Serum levels of sFas in @entity1 who later developed @entity295 were significantly increased at day 5 (P < 0.01) and day 9 (P < 0.05) after @entity130 compared with @entity1 with uneventful recovery. Apoptosis of @entity1 neutrophils was significantly decreased during the observation period compared with control cells. Moreover, Fas-mediated apoptosis of control neutrophils was efficiently inhibited by recombinant sFas and serum from septic @entity1 . Depletion of sFas from septic @entity1 sera diminished the antiapoptotic effects. In septic @entity1 , sFas levels were positively correlated with SOFA at day 1 (r = 0.7, P < 0.001), day 5 (r = 0.62, P < 0.01) and day 9 (r = 0.58, P < 0.01) and with @entity11891 and leukocyte counts (r = 0.49, P < 0.05 for both) as well as MODS at day 5 (r = 0.56, P < 0.01) after @entity130 . CONCLUSIONS: Increased sFas in @entity1 with @entity295 development impairs neutrophil extrinsic apoptosis and shows a positive correlation with the organ dysfunction scores and @entity11891 . Therefore, sFas might be a therapeutic target to prevent posttrauma hyperinflammation and @entity295 .
