Condron, C.,Neary, P.,Toomey, D.,Redmond, H. P.,Bouchier-Hayes, D.;

2003

Shock

Taurine attenuates calcium-dependent, Fas-mediated neutrophil apoptosis

Validated

()

19

66

564

569564

The pathway involved in Fas-mediated neutrophil apoptosis remains to be fully elucidated. We examined whether this pathway involved either oxygen-dependent or calcium-dependent mechanisms. We also investigated whether taurine, a powerful antioxidant and regulator of intracellular calcium fluxes, could inhibit Fas-mediated neutrophil apoptosis. Neutrophils were stimulated with Fas monoclonal antibody in the presence or absence of taurine. Fas receptor ligation resulted in significant neutrophil apoptosis at 18 h. Engagement of the Fas receptor rapidly resulted in a significant decrease in intracellular calcium. Apoptosis was inhibited and intracellular calcium levels were maintained in the presence of calcium ionophore A23187 or taurine. Fas ligation did not result in an increase in intracellular reactive oxygen species. We have demonstrated that Fas-mediated neutrophil apoptosis occurs after a decrease in intracellular calcium and is reactive oxygen intermediate independent. Furthermore, the amino acid taurine attenuates this pathway of neutrophil apoptosis by calcium regulation. This newly identified role of taurine in the inhibition of Fas-mediated neutrophil apoptosis may have significant implications for future manipulation of host pro-inflammatory cell function.The pathway involved in Fas-mediated neutrophil apoptosis remains to be fully elucidated. We examined whether this pathway involved either oxygen-dependent or calcium-dependent mechanisms. We also investigated whether taurine, a powerful antioxidant and regulator of intracellular calcium fluxes, could inhibit Fas-mediated neutrophil apoptosis. Neutrophils were stimulated with Fas monoclonal antibody in the presence or absence of taurine. Fas receptor ligation resulted in significant neutrophil apoptosis at 18 h. Engagement of the Fas receptor rapidly resulted in a significant decrease in intracellular calcium. Apoptosis was inhibited and intracellular calcium levels were maintained in the presence of calcium ionophore A23187 or taurine. Fas ligation did not result in an increase in intracellular reactive oxygen species. We have demonstrated that Fas-mediated neutrophil apoptosis occurs after a decrease in intracellular calcium and is reactive oxygen intermediate independent. Furthermore, the amino acid taurine attenuates this pathway of neutrophil apoptosis by calcium regulation. This newly identified role of taurine in the inhibition of Fas-mediated neutrophil apoptosis may have significant implications for future manipulation of host pro-inflammatory cell function.

1073-23221073-2322

://WOS:000183006900012://WOS:000183006900012