Shau H
Division of Surgical Oncology, UCLA Medical Center, Los Angeles, CA 90024.
J Immunol. 1988 Jul 1;141(1):234-40.
After being treated with rTNF, polymorphonuclear neutrophils (PMN) were highly suppressive to the growth of four different tumor target cells, Raji, K562, UCLA-SO-M14, and U937. Neutralizing TNF with specific antibodies before PMN were treated blocked induction of the anti-proliferative activity against Raji. However, after PMN were exposed to TNF the cytostatic activity could not be reversed by the antibody or by washing off TNF, indicating that the continuous presence of TNF was not required for expression of the anti-proliferative function. Addition of the hydrogen peroxide (HP) scavenger, catalase, at the beginning of the assay inhibited the cytostatic activity, suggesting that HP was involved in suppressing the tumor cell growth. In contrast, other reactive oxygen species inhibitors such as superoxide dismutase, sodium azide, L-methionine, or deferoxamine did not inhibit the cytostasis. HP alone at above 10 microM was cytostatic to Raji cells. The presence of TNF did not increase the sensitivity of Raji to HP. TNF activated PMN to produce HP but the amount of HP released in the culture supernatant was too low for direct cytostasis. PMN also became more adherent after TNF treatment. Therefore, the TNF-induced cytostasis may be mediated by local high concentrations of HP produced by PMN.
用重组肿瘤坏死因子（rTNF）处理后，多形核中性粒细胞（PMN）对四种不同的肿瘤靶细胞Raji、K562、UCLA-SO-M14和U937的生长具有高度抑制作用。在处理PMN之前用特异性抗体中和TNF可阻断对Raji的抗增殖活性的诱导。然而，在PMN暴露于TNF后，抗体或通过洗去TNF都无法逆转其细胞生长抑制活性，这表明抗增殖功能的表达不需要TNF持续存在。在测定开始时加入过氧化氢（HP）清除剂过氧化氢酶可抑制细胞生长抑制活性，提示HP参与抑制肿瘤细胞生长。相比之下，其他活性氧抑制剂如超氧化物歧化酶、叠氮化钠、L-甲硫氨酸或去铁胺并不抑制细胞生长抑制作用。单独的HP浓度高于10微摩尔/升时对Raji细胞具有细胞生长抑制作用。TNF的存在并未增加Raji对HP的敏感性。TNF激活PMN产生HP，但培养上清液中释放的HP量过低，无法直接产生细胞生长抑制作用。TNF处理后PMN的黏附性也增强。因此，TNF诱导的细胞生长抑制可能由PMN产生的局部高浓度HP介导。
