NITRIC-OXIDE SYNTHASE PATHWAY MAY MEDIATE HUMAN NATURAL-KILLER-CELL CYTOTOXICITY
NITRIC-OXIDE SYNTHASE PATHWAY MAY MEDIATE HUMAN NATURAL-KILLER-CELL CYTOTOXICITY
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DOI：
10.1111/j.1365-3083.1995.tb03687.x
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发表时间：
1995-11-01
影响因子：
3.7
通讯作者：
QURESHI, GA
中科院分区：
文献类型：
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作者：
XIAO, L;ENEROTH, PHE;QURESHI, GA
本研究证明，人体NK细胞效应机制引起靶细胞溶解对l -精氨酸有一定的需求。在只含有盐、缓冲系统和葡萄糖的缺陷培养基（DM）中，NK细胞介导的细胞毒性比在完全培养基（CM）中获得的细胞毒性降低了70%。而在DM中加入l -精氨酸可使NK细胞活性恢复到正常水平。CM的许多其他成分，如血清、谷氨酰胺和维生素，并没有改善DM中NK细胞介导的杀伤。当将除l-精氨酸外的所有氨基酸添加到DM中时，NK细胞功能性细胞溶解仅部分恢复。l -精氨酸增强NK细胞活性呈剂量依赖性。此外，诱导型和组成型一氧化氮合酶抑制剂n -单甲基- l-精氨酸（L-NMMA）在添加l-精氨酸的DM中抑制NK细胞溶解活性，表明一氧化氮（NO）的参与。结果还表明，l-精氨酸对人Mt细胞介导的细胞毒性的刺激作用伴随着亚硝酸盐和瓜氨酸积累的NO形成的增加。L-NMMA对NO的生成也有剂量依赖性的减少。亚硝酸盐和瓜氨酸的产生不仅与培养培养基中l-精氨酸的浓度相关，而且与NK细胞介导的细胞溶解能力增强相关。综上所述，这些发现可以确定人类NK细胞中l -精氨酸/ no相关的效应机制。在添加了添加剂的无l-精氨酸DM中，NK细胞介导的靶细胞杀伤没有形成亚硝酸盐和瓜氨酸。因此，似乎人类NK细胞可以通过no依赖性和非依赖性过程引起靶细胞杀伤。
The present study provides evidence that the human natural killer (NK) cell effector mechanism causing target cytolysis has a requirement for L-arginine. In a deficient medium (DM) containing only salts, buffer system and glucose, NK cell-mediated cytotoxicity was found to decrease by 70% as compared to that obtained in a complete medium (CM). However, adding L-arginine to such DM could restore the activity of NK cells to the normal level. Many other components of CM, such as serum, glutamine and vitamins did not improve NK cell-mediated killing in DM. When all amino acids except L-arginine were added to DM only a partial recovery of NK cell functional cytolysis was seen. L-arginine enhanced the NK cell activity in a dose-dependent manner. Additionally, the inhibitor of both inducible and constitutive nitric oxide synthase, N-monomethyl-L-arginine (L-NMMA) inhibited NK cytolytic activity in DM supplemented with L-arginine indicating participation of nitric oxide (NO). The results also show that the stimulatory effect of L-arginine on human Mt cell-mediated cytotoxicity was accompanied by an increase in NO formation as determined by accumulation of nitrite and citrulline. L-NMMA gave a dose-dependent reduction in NO generation as well. The nitrite and citrulline production dose-dependently correlated with not only the concentration of L-arginine in the cultivation medium, but also the enhanced NK cell-mediated cytolysis. Taken together, these findings could define a L-arginine/NO-linked effector mechanism in human NK cells. Nitrite and citrulline were not formed when NK cell-mediated target cell killing took place in a L-arginine-free DM supplemented with additives. Thus, it appears as if human NK cells may cause target cell killing via both NO-dependent and -independent processes.