Nitric oxide synthesis in the in vivo allograft response: a possible regulatory mechanism.
Nitric oxide synthesis in the in vivo allograft response: a possible regulatory mechanism.
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DOI：
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发表时间：
1991-08
期刊：
影响因子：
3.8
通讯作者：
Jan M. Langrehr;Rosemary A. Hoffman;T. Billiar;Kenneth K. Lee;Wolfgang H. Schraut;Simmons Rl
中科院分区：
文献类型：
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作者：
Jan M. Langrehr;Rosemary A. Hoffman;T. Billiar;Kenneth K. Lee;Wolfgang H. Schraut;Simmons Rl
已知活化的巨噬细胞将L-精氨酸氧化代谢为一氧化氮和瓜氨酸。我们最近发现，一氧化氮是一种有效的抑制分子在体外大鼠混合脾细胞培养，导致增殖抑制和细胞溶解性T细胞诱导。我们进行了这项研究，在大鼠海绵基质同种异体移植模型，以确定是否一氧化氮在体内同种异体移植反应中发挥作用。我们的实验表明，在移植后第6天，当首次检测到同种异体移植物浸润细胞的细胞溶解活性时，同种异体移植液含有比同基因移植液更高水平的NO2-/NO3-（一氧化氮代谢的稳定终产物）。此外，培养的移植物浸润细胞的上清液的评价显示，同种异体移植物浸润细胞自发地产生更高的量的一氧化氮比同基因移植物浸润细胞。一氧化氮产生的竞争性抑制剂NG-单甲基-L-精氨酸（NMA）的存在下，抑制一氧化氮的产生。大部分的一氧化氮生产中观察到的粘附巨噬细胞部分的同种异体移植物浸润细胞。当同种异体移植物浸润细胞在NMA存在下培养时，观察到供体特异性细胞溶解活性，而在NMA不存在下培养的同种异体移植物浸润细胞显示无细胞溶解活性。这些数据表明，一氧化氮的产生可能在同种异体移植反应中发挥重要的调节作用。
Activated macrophages are known to oxidatively metabolize L-arginine to nitric oxide and citrulline. We have recently shown that nitric oxide is a potent inhibitory molecule in the in vitro rat mixed-splenocyte culture, resulting in inhibition of proliferation and cytolytic T-cell induction. We undertook this study using the sponge matrix allograft model in the rat to determine whether nitric oxide plays a role in an in vivo allograft response. Our experiments showed that on day 6 after grafting, when cytolytic activity of allograft-infiltrating cells is first detected, allogeneic graft fluid contains higher levels of NO2-/NO3- (the stable endproducts of nitric oxide metabolism) than syngeneic graft fluid. Furthermore, evaluation of the supernatants of cultured graft-infiltrating cells revealed that allogeneic graft-infiltrating cells spontaneously produce higher amounts of nitric oxide than syngeneic graft-infiltrating cells. The nitric oxide production was inhibited in the presence of NG-monomethyl-L-arginine (NMA), the competitive inhibitor of nitric oxide production. Most of the nitric oxide production was observed in the adherent macrophage fraction of the allograft-infiltrating cells. When allograft-infiltrating cells were cultured in the presence of NMA, donor-specific cytolytic activity was observed, whereas allograft-infiltrating cells cultured in the absence of NMA showed no cytolytic activity. These data show that nitric oxide production may play an important regulatory role in the allograft response.