Shanahan F, Niederlehner A, MacDermott R P, Stenson W F, Kane M G, Targan S
Immunopharmacology. 1986 Apr;11(2):111-8. doi: 10.1016/0162-3109(86)90031-7.
Sulfasalazine and sulfapyridine but not 5-aminosalicylate inhibit spontaneous cytotoxicity mediated by human natural killer (NK) cells. The aim of this study was to determine which stage(s) of the NK cytotoxic reaction is inhibited by these compounds. Effector/target cell binding studies performed in parallel with cytotoxicity assays using purified large granular lymphocytes indicated that inhibition is a post-binding event. The kinetic profile of inhibition in a calcium pulse assay showed that inhibition continues long after the effector cell triggering stage and that although sulfasalazine may have some inhibitory effect on the calcium-dependent events of the programming phase, sulfapyridine continues to inhibit during the calcium-independent or lethal hit phase of the cytotoxic sequence. The NK soluble cytotoxic factor (NKCF) assay was used as a measure of the lethal hit since the time course of this assay permits study of the various substages of this terminal event in the lytic sequence. Sulfasalazine and sulfapyridine but not 5-aminosalicylate inhibited NKCF-mediated target cell lysis. Different substages of the NKCF-induced lytic reaction were affected by these agents. Sulfasalazine appears to inhibit binding of NKCF to the target cell whereas sulfapyridine predominantly inhibits early post-binding events.
柳氮磺胺吡啶和磺胺吡啶可抑制人自然杀伤（NK）细胞介导的自发细胞毒性，但5-氨基水杨酸无此作用。本研究旨在确定这些化合物抑制NK细胞毒性反应的哪些阶段。使用纯化的大颗粒淋巴细胞进行的效应细胞/靶细胞结合研究与细胞毒性测定平行进行，结果表明抑制作用发生在结合后阶段。钙脉冲试验中的抑制动力学曲线显示，在效应细胞触发阶段之后很长时间抑制作用仍持续存在，并且虽然柳氮磺胺吡啶可能对编程阶段的钙依赖性事件有一定抑制作用，但磺胺吡啶在细胞毒性序列的非钙依赖性或致死性打击阶段仍持续发挥抑制作用。由于该试验的时间进程允许研究裂解序列中这一终末事件的各个亚阶段，因此NK可溶性细胞毒性因子（NKCF）试验被用作致死性打击的指标。柳氮磺胺吡啶和磺胺吡啶可抑制NKCF介导的靶细胞裂解，但5-氨基水杨酸无此作用。这些药物对NKCF诱导的裂解反应的不同亚阶段有影响。柳氮磺胺吡啶似乎抑制NKCF与靶细胞的结合，而磺胺吡啶主要抑制结合后的早期事件。
