López-Collazo E, Hortelano S, Boscá L
Instituto de Bioquímica (Centro Mixto CSIC-UCM), Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
J Interferon Cytokine Res. 1998 Jul;18(7):461-7. doi: 10.1089/jir.1998.18.461.
Challenge of elicited peritoneal macrophages with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) was followed by an apoptotic response. These cells expressed cytokine-inducible nitric oxide synthase (iNOS) in response to these stimuli, and the NO released contributed markedly to the apoptotic death, as deduced from the increased viability observed when iNOS activity was inhibited. The antiviral type I IFN (IFN-alpha/beta) down-regulated the high levels of NO produced when cells were stimulated with suboptimal doses of LPS and IFN-gamma. Moreover, IFN-alpha/beta also decreased cell death in LPS/IFN-gamma-activated cells, as determined by the reduction in the content of oligonucleosomal DNA fragments, in the binding of annexin V to the plasma membrane, and in the amount of hypodiploid cells when analyzed by flow cytometry after in vivo staining with propidium iodide. Kinetic analysis of the protection exerted by IFN-alpha/beta) against the apoptosis induced by treatment with LPS and IFN-gamma showed that type I IFNs were very effective when added up to 1 h after IFN-gamma/LPS stimulation. Addition of IFN-alpha/beta 4 h after stimulation with IFN-gamma/LPS failed completely to prevent apoptosis. This inhibition of apoptosis elicited by IFN-alpha/beta suggests the existence of a mechanism intended to improve macrophage viability in the course of certain viral infections.
用脂多糖（LPS）和干扰素-γ（IFN-γ）刺激诱导的腹膜巨噬细胞后，会出现凋亡反应。这些细胞在对这些刺激的反应中表达细胞因子诱导型一氧化氮合酶（iNOS），并且从抑制iNOS活性时观察到的活力增加推断，释放的NO对凋亡死亡有显著贡献。抗病毒I型干扰素（IFN-α/β）下调了用次优剂量的LPS和IFN-γ刺激细胞时产生的高水平NO。此外，通过减少寡核小体DNA片段的含量、膜联蛋白V与质膜的结合以及用碘化丙啶体内染色后通过流式细胞术分析的亚二倍体细胞数量来确定，IFN-α/β也减少了LPS/IFN-γ激活细胞中的细胞死亡。对IFN-α/β对LPS和IFN-γ诱导的凋亡的保护作用进行动力学分析表明，在IFN-γ/LPS刺激后1小时内添加I型干扰素非常有效。在IFN-γ/LPS刺激4小时后添加IFN-α/β完全无法预防凋亡。IFN-α/β对凋亡的这种抑制表明存在一种旨在在某些病毒感染过程中提高巨噬细胞活力的机制。
