Histaminergic regulation of NK cells. Role of monocyte-derived reactive oxygen metabolites.
Histaminergic regulation of NK cells. Role of monocyte-derived reactive oxygen metabolites.
复制标题
NK 细胞的组胺能调节。
作者：
K. Hellstrand;A. Asea;C. Dahlgren;S. Hermodsson
通过离心淘洗回收的单核细胞可有效抑制体外人类 NK 细胞的功能。组胺通过单核细胞 H2 型组胺受体发挥作用，消除抑制信号。本研究的目的是明确单核细胞抑制 NK 细胞的组胺可逆机制，特别是单核细胞的呼吸爆发活性。从慢性肉芽肿性疾病患者中回收的单核细胞不会抑制 NK 细胞功能，表明单核细胞需要完整的烟酰胺腺嘌呤二核苷酸磷酸 (NAPDH) 氧化酶活性才能抑制 NK 细胞。此外，过氧化氢酶（一种过氧化氢 (H2O2) 的清除剂）被发现可以有效逆转单核细胞诱导的 NK 细胞功能抑制；另一方面，超氧化物歧化酶（超氧阴离子的清除剂）、羟自由基清除剂如甘露醇和去铁胺、次氯酸清除剂牛磺酸或一氧化氮合成酶抑制剂NG-单甲基-L-精氨酸（L-NMMA）不会影响单核细胞来源的抑制信号。微摩尔浓度的 H2O2 重建了单核细胞对 NK 细胞功能的抑制作用。组胺没有清除活性，但能有效抑制分离单核细胞中 H2O2 的产生。组胺的这种作用是由 H2 型组胺受体转导的。我们得出的结论是，淘析的单核细胞对 NK 细胞的组胺可逆抑制作用取决于单核细胞活性氧代谢物的形成，并且 H2O2 是抑制信号的关键介质。
Monocytes, recovered by centrifugal elutriation, effectively inhibit functions of human NK cells in vitro. Histamine, acting via monocyte H2-type histamine receptors, abrogates the inhibitory signal. The aim of this study was to define the histamine-reversible mechanism by which monocytes inhibit NK cells with special reference to the respiratory burst activity of monocytes. Monocytes recovered from patients with chronic granulomatous disease did not suppress NK cell function, indicating the requirement of intact nicotinamide-adenine dinucleotide phosphate (NAPDH) oxidase activity of monocytes to inhibit NK cells. Furthermore, catalase, a scavenger of hydrogen peroxide (H2O2), was found to potently reverse the monocyte-induced inhibition of NK cell function; on the other hand, superoxide dismutase (a scavenger of superoxide anion), hydroxyl radical scavengers such as mannitol and deferoxamine, the hypochlorous acid scavenger taurin, or the nitric oxide synthetase inhibitor NG-monomethyl-L-arginine (L-NMMA) did not affect the monocyte-derived, suppressive signal. H2O2, at micromolar concentrations, reconstituted the inhibitory effects of monocytes on NK cell function. Histamine had no scavenger activity but effectively suppressed the generation of H2O2 in isolated monocytes. This effect of histamine was transduced by H2-type histamine receptors. We conclude that the histamine-reversible, inhibitory effect of elutriated monocytes on NK cells is dependent on the formation of reactive oxygen metabolites by monocytes and that H2O2 is a pivotal mediator of the suppressive signal.