Hypoxic Regulation of Neutrophil Apoptosis Role: of Reactive Oxygen Intermediates in Constitutive and Tumor Necrosis Factor ?-Induced Cell Death
Activation of the NADPH oxidase system to generate reactive oxygen species (ROS) plays a key role in bacterial killing by human neutrophils. However, the involvement of such radicals in spontaneous and TNF?-driven neutrophil apoptosis remains uncertain. While incubation of cells under anoxic conditions attenuated the pro-apoptotic effect of TNF?, full activation of the respiratory burst using PAF followed by fMLP, or the addition of physiologically relevant concentrations of H2O2, had no effect on the rate of apoptosis. Furthermore, the phosphoinositide 3-kinase inhibitor, LY294002, which abolishes receptor-mediated activation of the NADPH oxidase, and five discrete anti-oxidants all failed to affect apoptotic thresholds. Thus ROS do not appear to modulate constitutive apoptosis in neutrophils or appear sufficient to mediate the pro-apoptotic effect of TNF?.
neutrophils apoptosis nadph oxidase tnf?