Walker B A, Hagenlocker B E, Stubbs E B, Sandborg R R, Agranoff B W, Ward P A
Department of Pathology, University of Michigan School of Medicine, Ann Arbor 48109-0602.
J Immunol. 1991 Jan 15;146(2):735-41.
Signal transduction events have been evaluated in human neutrophils stimulated with immune complexes consisting of polyclonal rabbit antibody complexed with BSA. Immune complexes induced dose-related O2- responses, but very small increases in intracellular calcium ([Ca2+]i) levels were observed, in contrast to FMLP-stimulated cells. Measurements employing [45Ca2+] demonstrated that calcium influx and efflux in cells stimulated with immune complexes was substantially less than fluxes found in FMLP-stimulated cells. With respect to inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) formation under conditions in which the O2- responses to immune complexes or FMLP were similar, the Ins(1,4,5)P3 response to immune complexes was much smaller (by 65%) as compared to that induced by FMLP. Although pertussis toxin-treated cells showed a greatly diminished O2- response (by 89%) to FMLP, the response to immune complexes was largely resistant (only 26% reduction) to the inhibitory effects of this toxin. Antibodies to Fc gamma R indicated that engagement of Fc gamma RII and Fc gamma RIII, but not Fc gamma RI, receptors was related to the O2- response of neutrophils to immune complexes. O2- formation occurred in neutrophils incubated with Staphylococcus aureus cell walls bearing antibodies to Fc gamma RII or Fc gamma RIII. These data indicate that, in human neutrophils stimulated with immune complexes, signal transduction events involve engagement of Fc gamma RII and Fc gamma RIII. The O2- response is largely pertussis-toxin insensitive, is not associated with a significant increase in levels of [Ca2+]i, and is associated with relatively little formation of Ins(1,4,5)P3. This is in contrast to cells stimulated with FMLP in which O2- responses are largely pertussis toxin-sensitive and associated with large increases in [Ca2+]i as well as formation of Ins(1,4,5)P3. Signal transduction events involving Fc gamma R appear to be quite different from those events related to engagement of FMLP receptors.
已在用与牛血清白蛋白复合的多克隆兔抗体组成的免疫复合物刺激的人中性粒细胞中评估了信号转导事件。免疫复合物诱导了剂量相关的超氧阴离子（O₂⁻）反应，但与佛波醇甲脂（FMLP）刺激的细胞相比，观察到细胞内钙（[Ca²⁺]i）水平仅有非常小的升高。采用[⁴⁵Ca²⁺]的测量表明，免疫复合物刺激的细胞中的钙流入和流出明显少于FMLP刺激的细胞中的通量。在对免疫复合物或FMLP的O₂⁻反应相似的条件下，就肌醇1,4,5 - 三磷酸（Ins(1,4,5)P₃）形成而言，与FMLP诱导的相比，免疫复合物诱导的Ins(1,4,5)P₃反应要小得多（减少65%）。尽管百日咳毒素处理的细胞对FMLP的O₂⁻反应大大减弱（减少89%），但对免疫复合物的反应在很大程度上对该毒素的抑制作用具有抗性（仅减少26%）。针对FcγR的抗体表明，FcγRII和FcγRIII（而非FcγRI）受体的结合与中性粒细胞对免疫复合物的O₂⁻反应有关。在用带有针对FcγRII或FcγRIII抗体的金黄色葡萄球菌细胞壁孵育的中性粒细胞中发生了O₂⁻形成。这些数据表明，在用免疫复合物刺激的人中性粒细胞中，信号转导事件涉及FcγRII和FcγRIII的结合。O₂⁻反应在很大程度上对百日咳毒素不敏感，与[Ca²⁺]i水平的显著升高无关，并且与Ins(1,4,5)P₃的形成相对较少有关。这与FMLP刺激的细胞形成对比，在FMLP刺激的细胞中，O₂⁻反应在很大程度上对百日咳毒素敏感，并且与[Ca²⁺]i的大幅升高以及Ins(1,4,5)P₃的形成有关。涉及FcγR的信号转导事件似乎与那些与FMLP受体结合相关的事件有很大不同。
