Murray J, Walmsley S R, Mecklenburgh K I, Cowburn A S, White J F, Rossi A G, Chilvers E R
Respiratory Medicine Division, Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's and Papworth Hospitals, Cambridge CB2 2QQ, UK.
Ann N Y Acad Sci. 2003 Dec;1010:417-25. doi: 10.1196/annals.1299.075.
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 TNFalpha-driven neutrophil apoptosis remains uncertain. While incubation of cells under anoxic conditions attenuated the pro-apoptotic effect of TNFalpha, full activation of the respiratory burst using PAF followed by fMLP, or the addition of physiologically relevant concentrations of H(2)O(2), 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 TNFalpha.
激活NADPH氧化酶系统以产生活性氧（ROS）在人类中性粒细胞杀灭细菌过程中起关键作用。然而，此类自由基在自发性和TNFα驱动的中性粒细胞凋亡中的作用仍不确定。虽然在缺氧条件下孵育细胞可减弱TNFα的促凋亡作用，但使用PAF随后fMLP使呼吸爆发完全激活，或添加生理相关浓度的H₂O₂，对凋亡速率均无影响。此外，磷酸肌醇3-激酶抑制剂LY294002可消除受体介导的NADPH氧化酶激活，以及五种不同的抗氧化剂均未能影响凋亡阈值。因此，ROS似乎不会调节中性粒细胞的组成性凋亡，也似乎不足以介导TNFα的促凋亡作用。
