Nair M P, Schwartz S A
Cell Immunol. 1983 Oct 1;81(1):45-60. doi: 10.1016/0008-8749(83)90210-1.
The in vitro effect of histamine and its antagonists, cimetidine and clemastine fumarate, on natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) activities of human lymphocytes was investigated. The histamine 1 (H1) antagonist, clemastine fumarate, and the histamine 2 (H2) antagonist, cimetidine, but not histamine alone, inhibited the NK and ADCC activities of lymphocytes when added directly to the mixture of effector and target cells in a 51Cr-release assay. This inhibition was proportional to the concentration of drugs added and was observed at various effector to target ratios against several targets. H1 and H2 antagonists also inhibited NK activities of T cells as well as Percoll-separated, NK-enriched effector cells. The inhibition was significantly reversed by histamine. In target binding assays, clemastine fumarate and cimetidine also decreased the target binding capacity of effector lymphocytes. Further, PBL precultured with histamine (10(-3)-10(-4) M) for 24 hr showed a significant decrease in their NK and ADCC activities. In coculture experiments, PBL precultured with histamine suppressed the NK activity of normal autologous effector lymphocytes. PBL precultured with histamine showed an increased number of OKT8+ cells, as estimated using monoclonal antibodies. The suppression of cytotoxicity was not due to either direct toxicity, steric hindrance, crowding, or cell death, but by functionally viable suppressor cells. An immunoregulatory role for histamine in NK and ADCC reactions is proposed.
研究了组胺及其拮抗剂西咪替丁和富马酸氯马斯汀对人淋巴细胞自然杀伤（NK）和抗体依赖性细胞毒性（ADCC）活性的体外作用。在51Cr释放试验中，当直接将组胺1（H1）拮抗剂富马酸氯马斯汀和组胺2（H2）拮抗剂西咪替丁添加到效应细胞和靶细胞的混合物中时，它们会抑制淋巴细胞的NK和ADCC活性，但单独的组胺则不会。这种抑制作用与添加药物的浓度成正比，并且在针对多个靶标的不同效应细胞与靶细胞比例下均能观察到。H1和H2拮抗剂还抑制T细胞以及经Percoll分离的、富含NK的效应细胞的NK活性。组胺可显著逆转这种抑制作用。在靶细胞结合试验中，富马酸氯马斯汀和西咪替丁也降低了效应淋巴细胞的靶细胞结合能力。此外，用组胺（10^(-3)-10^(-4) M）预培养24小时的外周血淋巴细胞（PBL）其NK和ADCC活性显著降低。在共培养实验中，用组胺预培养的PBL抑制了正常自体效应淋巴细胞的NK活性。用单克隆抗体估计，用组胺预培养的PBL显示OKT8+细胞数量增加。细胞毒性的抑制不是由于直接毒性、空间位阻、拥挤或细胞死亡，而是由于功能上有活力的抑制细胞。提出了组胺在NK和ADCC反应中的免疫调节作用。
