Munakata T, Semba U, Shibuya Y, Kuwano K, Akagi M, Arai S
J Immunol. 1985 Apr;134(4):2449-55.
Interferon (IFN)-inducing activity of hydrogen peroxide in human peripheral mononuclear cells was investigated. Among the mononuclear cells, purified nonadherent cells produced IFN, but not B cells and monocytes. The maximal titer of IFN by purified nonadherent cells was observed after a 72-hr cultivation in the presence of 10(-2) mM H2O2 without affecting their viability. Furthermore, the purified nonadherent cells, but not the unpurified mononuclear cells, showed an augmented cytotoxicity to K562 when stimulated with hydrogen peroxide. By using Percoll discontinuous density gradient centrifugation, peripheral blood nonphagocytic and nonadherent mononuclear cells were divided into the low and high density fractions for which natural killer (NK) cells and T cells were enriched, respectively. The NK-enriched low density fractions, but not the T cell-enriched high density fractions, showed IFN production by the stimulation of hydrogen peroxide. IFN production as well as large granular lymphocytes and HNK-1+, Leu-11+ cells of the NK-enriched fractions were abrogated by treatment of the cells with monoclonal antibody against human NK cells (HNK-1+) but not against T cells (OKT3) in the presence of complement. Moreover, hydrogen peroxide-inducing IFN production seems to be regulated by monocytes. The antiserum neutralizing IFN-alpha and IFN-beta failed to neutralize substantially IFN-produced NK cells. The treatment with either pH 2 or antiserum-neutralizing human IFN-gamma resulted in marked reduction, indicating that a major part of IFN was IFN-gamma. The purified nonadherent cells showed IFN production and augmented cytotoxicity when cultured separately from activated macrophages by opsonized zymosan; furthermore, both IFN production and enhancement of cytotoxicity were abrogated by catalase. These results suggest that both exogenous and endogenous hydrogen peroxide might be responsible for a part of immunoregulation.
研究了过氧化氢在人外周血单个核细胞中诱导干扰素（IFN）的活性。在单个核细胞中，纯化的非贴壁细胞可产生IFN，但B细胞和单核细胞则不能。在存在10(-2) mM H2O2的情况下培养72小时后，纯化的非贴壁细胞产生的IFN达到最大滴度，且不影响其活力。此外，纯化的非贴壁细胞，而非未纯化的单个核细胞，在用过氧化氢刺激后对K562细胞的细胞毒性增强。通过使用Percoll不连续密度梯度离心法，外周血非吞噬性和非贴壁单个核细胞被分为低密度和高密度组分，其中分别富集了自然杀伤（NK）细胞和T细胞。富含NK的低密度组分，而非富含T细胞的高密度组分，在过氧化氢刺激下可产生IFN。在补体存在的情况下，用抗人NK细胞（HNK-1+）而非抗T细胞（OKT3）的单克隆抗体处理富含NK的组分细胞后，IFN的产生以及大颗粒淋巴细胞和HNK-1+、Leu-11+细胞均被消除。此外，过氧化氢诱导IFN产生似乎受单核细胞调节。中和IFN-α和IFN-β的抗血清未能有效中和NK细胞产生的IFN。用pH 2或中和人IFN-γ的抗血清处理后导致显著降低，表明大部分IFN为IFN-γ。当与经调理的酵母聚糖激活的巨噬细胞分开培养时，纯化的非贴壁细胞可产生IFN并增强细胞毒性；此外，过氧化氢酶可消除IFN的产生和细胞毒性的增强。这些结果表明，外源性和内源性过氧化氢可能都参与了部分免疫调节。
