Langrehr J M, Hoffman R A, Billiar T R, Lee K K, Schraut W H, Simmons R L
Department of Surgery, University of Pittsburgh, PA 15261.
Surgery. 1991 Aug;110(2):335-42.
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.
已知活化的巨噬细胞可将L-精氨酸氧化代谢为一氧化氮和瓜氨酸。我们最近发现，一氧化氮在体外大鼠混合脾细胞培养中是一种有效的抑制分子，可导致增殖抑制和细胞毒性T细胞诱导受抑。我们采用大鼠海绵基质同种异体移植模型进行了这项研究，以确定一氧化氮在体内同种异体移植反应中是否起作用。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浸润细胞的细胞溶解活性时，同种异体移植液中NO2-/NO3-（一氧化氮代谢的稳定终产物）的水平高于同基因移植液。此外，对培养的移植浸润细胞上清液的评估显示，同种异体移植浸润细胞比同基因移植浸润细胞自发产生更多的一氧化氮。在一氧化氮产生的竞争性抑制剂NG-单甲基-L-精氨酸（NMA）存在的情况下，一氧化氮的产生受到抑制。大部分一氧化氮产生见于同种异体移植浸润细胞的贴壁巨噬细胞部分。当同种异体移植浸润细胞在NMA存在的情况下培养时，可观察到供体特异性细胞溶解活性，而在不存在NMA的情况下培养的同种异体移植浸润细胞则未显示细胞溶解活性。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起重要的调节作用。
