Augmentation of an antitumor CTL response In vivo by inhibition of suppressor macrophage nitric oxide.
Augmentation of an antitumor CTL response In vivo by inhibition of suppressor macrophage nitric oxide.
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DOI：
10.4049/jimmunol.163.11.5877
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发表时间：
1999-12
影响因子：
4.4
通讯作者：
Marianne Medot-Pirenne;M. Heilman;Malinee Saxena;Patricia E. McDermott;Charles D. Mills
中科院分区：
文献类型：
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作者：
Marianne Medot-Pirenne;M. Heilman;Malinee Saxena;Patricia E. McDermott;Charles D. Mills
提供的证据表明，抑制巨噬细胞NO的产生可以增加体内CTL反应。具体地，通过渗透泵给予NG-单甲基-L -精氨酸（NGMMA）增加了预免疫小鼠腹腔中针对P815肥大细胞瘤的肿瘤特异性CTL应答。CTL应答的幅度和持续时间均增加。NGMA处理小鼠的巨噬细胞NO产生减少，这一发现支持了抑制NO合酶途径导致CTL应答增强。此外，在体外抑制NO生产的腹膜渗出细胞从P815肿瘤攻击的小鼠增强观察到的次级CTL反应。在这些培养物中，NGMMA增强了细胞增殖，表明巨噬细胞NO可能通过抑制克隆扩增来抑制CTL。在该实验系统中，在体内观察到NO介导的抑制，即使CTL应答没有被抑制，因为发生了肿瘤排斥。因此，目前的结果是一致的结论，即巨噬细胞NO介导的抑制CTL反应是活化巨噬细胞的副作用，而不是从一个独特的子集的长期以来一直被称为抑制巨噬细胞的作用。最重要的是，结果表明，NO介导的抑制巨噬细胞活性可以是一个重要的CTL免疫调节元件在体内。
Evidence is provided that inhibition of macrophage NO production can augment in vivo CTL responses. Specifically, administration of NG-monomethyl-l -arginine (NGMMA) via osmotic pumps increases the tumor-specific CTL response against the P815 mastocytoma in the peritoneal cavity of preimmunized mice. Both the magnitude and duration of the CTL response were increased. That the augmented CTL response resulted from inhibition of the NO synthase pathway is supported by the finding that macrophage NO production from NGMMA-treated mice was reduced. Also, in vitro inhibition of NO production by peritoneal exudate cells from P815 tumor-challenged mice augmented the secondary CTL response observed. Cell proliferation was augmented by NGMMA in these cultures, suggesting that macrophage NO may suppress CTL by inhibiting clonal expansion. NO-mediated inhibition was observed in vivo in this experimental system, even though the CTL response is not suppressed, in that tumor rejection occurs. Therefore, the present results are consistent with the conclusion that macrophage NO-mediated inhibition of the CTL response is a side effect of activating macrophages rather than resulting from the action of a distinct subset of what have long been termed suppressor macrophages. Most important, the results indicate that NO-mediated suppressor macrophage activity can be an important CTL immunoregulatory element in vivo.