Shau H Y, Golub S H
Division of Surgical Oncology, UCLA School of Medicine, Los Angeles, CA 90024.
J Immunol. 1989 Aug 1;143(3):1066-72.
Peripheral blood polymorphonuclear neutrophils (PMN) can significantly inhibit lymphokine-activated killer- (LAK) mediated cytotoxicity when added to a cytotoxicity assay of IL-2-activated PBL and target cells. The inhibition by resting PMN is resistant to blocking with catalase and superoxide dismutase, suggesting that reactive oxygen species are not involved. The addition of TNF greatly enhanced the PMN-mediated inhibition of LAK effector functions. This TNF-enhanced inhibition is reversed by catalase, but not by superoxide dismutase, implicating hydrogen peroxide in the augmented inhibition. Separation of PMN from effector cells and target cells totally abrogates the inhibition by both resting PMN and TNF-treated PMN. Formalin-fixed PMN, heat-treated PMN, PMN lysates, and PMN membrane all fail to mediate any inhibition of LAK. These results suggest that contact with intact viable PMN is needed for inducing LAK inhibition. However, pretreatment of LAK cells with PMN also decreases their cytotoxicity in subsequent chromium release assays. PMN can also inhibit NK cytotoxicity of fresh PBL. However, NK activity is much less sensitive to inhibition by resting PMN than is LAK. TNF also augments PMN inhibition of NK, and there is no significant difference between LAK and NK in sensitivity to the TNF-enhanced inhibition. Our results indicate that PMN can significantly influence the destruction of tumor targets by LAK and NK, and suggest that approaches to circumvent such regulation may be important in the outcome of immunotherapies with IL-2 and LAK cells.
当将外周血多形核中性粒细胞（PMN）添加到白细胞介素-2激活的外周血淋巴细胞（PBL）与靶细胞的细胞毒性试验中时，它能显著抑制淋巴因子激活的杀伤细胞（LAK）介导的细胞毒性。静息PMN的抑制作用不受过氧化氢酶和超氧化物歧化酶阻断的影响，这表明活性氧物质未参与其中。肿瘤坏死因子（TNF）的添加极大地增强了PMN介导的对LAK效应器功能的抑制作用。这种TNF增强的抑制作用可被过氧化氢酶逆转，但不能被超氧化物歧化酶逆转，这表明过氧化氢参与了增强的抑制作用。将PMN与效应细胞和靶细胞分离完全消除了静息PMN和TNF处理的PMN的抑制作用。甲醛固定的PMN、热处理的PMN、PMN裂解物和PMN膜均不能介导对LAK的任何抑制作用。这些结果表明，诱导LAK抑制需要与完整存活的PMN接触。然而，用PMN预处理LAK细胞也会在随后的铬释放试验中降低其细胞毒性。PMN还能抑制新鲜PBL的自然杀伤细胞（NK）细胞毒性。然而，NK活性对静息PMN抑制的敏感性远低于LAK。TNF也增强了PMN对NK的抑制作用，并且LAK和NK对TNF增强抑制的敏感性没有显著差异。我们的结果表明，PMN能显著影响LAK和NK对肿瘤靶标的破坏，并表明规避这种调节的方法可能对白细胞介素-2和LAK细胞免疫治疗的结果很重要。
