CROSS LINKING OF CLASS II MOLECULES AS A SIGNAL IN REGULATION OF MONOCYTES

人淘析器纯化的单核细胞与抗HLA-DR或DQ的孵育 抗体抑制血清诱导的花生四烯酸释放， 经处理的酵母聚糖（STZ），一种已知诱导 肌醇磷脂水解和Ca = 2内流。 然而，只有反- HLA-Dr抗体部分抑制STZ诱导的磷酸肌醇 水解和伴刀豆球蛋白-A诱导的Ca +2内流。 孵育 抗HLA-Dr或DQ抗体抑制佛波酯诱导的AA释放， 以及超氧化物产生和IL-1释放。 单核细胞抑制 抗II类抗体的作用不伴随cAMP 提升 此外，加入外源性db-cAMP和其他试剂， （毛喉素，霍乱毒素，或IBMX），可以增加cAMP水平 通过不同的机制，单独或与抗HLA联合 抗体对因子释放无抑制作用。 我们的结果 证明II类分子的扰动下调细胞 在信号转导途径的多个点激活 主要抑制磷酸肌醇水解。 他们 还表明抗HLA II类抗体的抑制作用是 可能不是通过cAMP升高介导的。

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 which is known to induce inositol phospholipid hydrolysis and Ca=2 influx. However, only anti- HLA-Dr antibody partially inhibited STZ-induced inositol phosphate hydrolysis and concanavalin-A- induced Ca+2 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 IBMX) that can 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 phosphate hydrolysis. They also suggest that the inhibition by anti-HLA class II antibody is probably not mediated via cAMP elevation.