Puri J, Taplits M, Alava M, Bonvini E, Hoffman T
Division of Hematology, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland 20892.
Inflammation. 1992 Feb;16(1):31-44. doi: 10.1007/BF00917513.
Incubation of human elutriator-purified monocytes with anti-HLA-DR or DQ antibody inhibited the release of arachidonic acid induced by serum-treated zymosan (STZ), a phagocytic stimulus that is known to induce inositol phospholipid hydrolysis and Ca2+ influx. However, only anti-HLA-DR antibody partially inhibited STZ-induced inositol phospholipid hydrolysis and concanavalin-A-induced Ca2+ influx. Incubation with anti-HLA-DR or -DQ antibody inhibited phorbol ester-induced AA release as well as superoxide production and IL-1 release. Inhibition of monocyte function by anti-class II antibodies was not accompanied by cAMP elevation. Furthermore, addition of exogenous db-cAMP and other agents (forskolin, cholera toxin, or 3-isobutyl-1-methyl-xanthine) that increase cAMP levels through different mechanisms, alone or in combination with anti-HLA antibodies, had no inhibitory effect on factor release. Our results demonstrate that perturbation of class II molecules down-modulates cell activation at more than one point of the signal transduction pathway with dominant inhibition distal to inositol phospholipid hydrolysis. They also suggest that the inhibition by anti-HLA class II antibody is probably not mediated via cAMP elevation.
用人淘洗纯化的单核细胞与抗 HLA - DR 或 DQ 抗体孵育，可抑制血清处理的酵母聚糖（STZ）诱导的花生四烯酸释放。STZ 是一种吞噬刺激物，已知可诱导肌醇磷脂水解和 Ca²⁺内流。然而，只有抗 HLA - DR 抗体部分抑制 STZ 诱导的肌醇磷脂水解和伴刀豆球蛋白 A 诱导的 Ca²⁺内流。与抗 HLA - DR 或 - DQ 抗体孵育可抑制佛波酯诱导的花生四烯酸释放以及超氧化物生成和白细胞介素 - 1 释放。抗 II 类抗体对单核细胞功能的抑制并未伴随 cAMP 升高。此外，添加外源性二丁酰环磷腺苷（db - cAMP）以及通过不同机制增加 cAMP 水平的其他试剂（福斯可林、霍乱毒素或 3 - 异丁基 - 1 - 甲基黄嘌呤），单独或与抗 HLA 抗体联合使用，对因子释放均无抑制作用。我们的结果表明，II 类分子的扰动在信号转导途径的多个点下调细胞活化，在肌醇磷脂水解远端具有主要抑制作用。它们还表明，抗 HLA II 类抗体的抑制作用可能不是通过 cAMP 升高介导的。
