Hellstrand K, Hermodsson S
Department of Virology, University of Göteborg, Sweden.
Int Arch Allergy Appl Immunol. 1987;84(3):247-55. doi: 10.1159/000234431.
In this study we investigated the modulation of natural killer (NK) cell activity by various histamine receptor antagonists in vitro. The histamine H2-receptor antagonists cimetidine, ranitidine and tiotidine suppressed NK cell cytotoxicity (NKCC) at a high concentration (10(-3) M). Cimetidine enhanced NKCC of Ficoll-Hypaque-separated lymphocytes and of lymphocytes enriched for NKCC by Percoll density gradient centrifugation. The enhancing effect of cimetidine was dose-dependent at final concentrations of 10(-4)-10(-7) M and did not require the presence of adherent cells/monocytes. Ranitidine did not affect NKCC over a wide range of concentrations. Tiotidine strongly enhanced NKCC of low-density, large granular lymphocyte-enriched mononuclear cells (MNC) in the presence of adherent cells/monocytes, but was ineffective in nonadherent effector cells. All H2-receptor antagonists clearly antagonized histamine-induced NKCC enhancement in monocyte-containing effector cells. Clemastin, a specific H1-receptor antagonist, effectively suppressed NKCC. This effect was mimicked by a clemastin isomer with very low affinity for H1-receptors. We conclude that (1) cimetidine enhances NKCC in vitro by a mechanism of action that is not specifically related to antagonism of H2-receptors, (2) tiotidine displays mixed agonist/antagonist properties for MNC H2-receptors and (3) NK-suppressive properties of clemastin are unrelated to H1-receptor antagonism.
在本研究中，我们在体外研究了各种组胺受体拮抗剂对自然杀伤（NK）细胞活性的调节作用。组胺H2受体拮抗剂西咪替丁、雷尼替丁和替奥替丁在高浓度（10⁻³ M）时可抑制NK细胞细胞毒性（NKCC）。西咪替丁增强了经Ficoll-Hypaque分离的淋巴细胞以及通过Percoll密度梯度离心富集NKCC的淋巴细胞的NKCC。西咪替丁的增强作用在终浓度为10⁻⁴ - 10⁻⁷ M时呈剂量依赖性，且不需要贴壁细胞/单核细胞的存在。雷尼替丁在很宽的浓度范围内不影响NKCC。替奥替丁在有贴壁细胞/单核细胞存在时，强烈增强低密度、富含大颗粒淋巴细胞的单核细胞（MNC）的NKCC，但对非贴壁效应细胞无效。所有H2受体拮抗剂均明显拮抗组胺诱导的含单核细胞效应细胞中NKCC的增强。氯马斯汀，一种特异性H1受体拮抗剂，有效抑制NKCC。这种作用被一种对H1受体亲和力极低的氯马斯汀异构体模拟。我们得出结论：（1）西咪替丁在体外通过一种与H2受体拮抗作用无特异性关系的作用机制增强NKCC；（2）替奥替丁对MNC的H2受体表现出混合激动剂/拮抗剂特性；（3）氯马斯汀的NK抑制特性与H1受体拮抗作用无关。
