INTERFERON-?? INHIBITS CASPASE-3 ACTIVITY IN POST-INJURY NEUTROPHILS

Abstract

Interferon-γ (IFN) is known to enhance several neutrophil (PMN) functions as well as exert an antiapoptotic effect through the inhibition of specific caspases. Trauma has been reported to alter PMN cytokine responses and apoptosis. We hypothesize that trauma alters IFN inhibited PMN apoptosis and Caspase-3 activity. To test this PMN's from control or critically injured subjects after traumatic shock were incubated in medium alone or medium with IFN (100 units/ml). PMN apoptosis was assayed with Annexin V staining and Caspase-3 activity was detected by flow cytometry using a FITC-labeled antibody. Data are presented as net mean flouroescent intensity.TableIFN inhibited PMN apoptosis in healthy controls. (LPS was used a positive control) IFN further inhibited PMN apoptosis in trauma patients. Caspase 3 activity was significantly inhibited in IFN stimulated normal subject PMN. In addition, caspase 3 activity was inhibited in trauma patient PMN and further inhibited in IFN treated trauma patient PMN. These data demonstrate that the apoptosis of circulating PMN following major injury is responsive to IFN. Furthermore, IFN specifically inhibits caspase-3 in human PMN. The inhibited activity of caspase-3 may contribute to IFN mediated antiapoptotic effects in both control and post-injury PMN. IFN may induce the production of intracellular proteins which up or down regulate PMN apoptosis such as Bcl-XL, inhibitor of apoptosis family members, or survivin. The results suggest that IFN-γ may contribute not only to augmented host defense against microorganisms but also increased tissue damage at inflammatory sites after shock by delayed PMN apoptosis.