Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells.
Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells.
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DOI：
10.1084/jem.169.5.1543
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发表时间：
1989-05-01
期刊：
影响因子：
--
通讯作者：
Nathan CF
中科院分区：
文献类型：
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作者：
Stuehr DJ;Nathan CF
活化的巨噬细胞 (M phi) 的代谢途径涉及 L-精氨酸的胍基氮的氧化，这是抑制某些靶细胞的生长和呼吸所必需的。本研究的目的是确定引起这些损伤的 M phi 代谢物。 L-精氨酸途径的稳定产物NO2-和NO3-在共培养条件下不能引起细胞停滞。然而，NO2- 在轻度酸化后会产生细胞抑制作用，这有利于其转化为更具反应性的氮氧化物。这表明NO。 （和/或 NO2），最近被鉴定为 L-精氨酸的 M phi 代谢物，可能是一种介质。正品编号以剂量依赖性方式引起 L1210 细胞的细胞生长抑制和呼吸抑制。 NO引起的线粒体损伤。仅限于复合体 1 和 2，这种损伤模式与与活化的 M phi 共培养后观察到的损伤模式相同。包含 NO。清除剂系统可防止 M phi-L1210 共培养物中发生细胞停滞。因此，M phi-生成NO。可以解释 L-精氨酸依赖性细胞抑制和呼吸抑制。
A metabolic pathway of activated macrophages (M phi) involving oxidation of the guanido nitrogens of L-arginine is required for inhibition of growth and respiration of some target cells. The goal of this study was to identify the M phi metabolite(s) that induce these injuries. The stable products of the L-arginine pathway, NO2- and NO3-, were incapable of causing cytostasis under coculture conditions. However, NO2- became cytostatic upon mild acidification, which favors its transformation into nitrogen oxides of greater reactivity. This suggested that NO. (and/or NO2), recently identified as an M phi metabolite of L-arginine, could be a mediator. Authentic NO. caused cytostasis and respiratory inhibition in L1210 cells in a dose- dependent manner. The mitochondrial lesions caused by NO. were confined to complex 1 and 2, a pattern of injury identical to that seen after coculture with activated M phi. Inclusion of NO. scavenger systems prevented cytostasis from developing in M phi-L1210 cocultures. Thus, M phi-generated NO. can account for L-arginine-dependent cytostasis and respiratory inhibition.