Immune complex-stimulated neutrophil LTB4 production is dependent on beta 2 integrins.
Immune complex-stimulated neutrophil LTB4 production is dependent on beta 2 integrins.
复制标题
免疫复合物刺激的中性粒细胞LTB4产生取决于β2整合素。
DOI：
10.1083/jcb.120.6.1509
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发表时间：
1993-03
影响因子：
7.8
通讯作者：
Brown, E J
中科院分区：
文献类型：
--
作者：
Graham, I L;Lefkowith, J B;Anderson, D C;Brown, E J
β 2整联蛋白（LFA-1、Mac-1和p150，95）对白细胞的许多粘附功能至关重要。尽管IgG调理颗粒的结合通常在不存在β 2整联蛋白的情况下发生，但活化的中性粒细胞（PMN）对IgG调理颗粒的吞噬作用需要这些整联蛋白。这一观察结果表明β 2整合素在颗粒结合后的吞噬作用中的作用。为了研究β 2整联蛋白参与IgG介导的功能的机制，我们检测了β 2整联蛋白在粘附至免疫复合物（IC）包被的表面中的作用。在对照和β 2缺乏的吞噬细胞中，IC包被表面上的初始粘附和扩散是等同的。然而，遗传性β 2缺陷型PMN和用抗β 2 mAb IB 4处理的PMN随后都从IC包被的表面脱离。为了确定IgG活化的生物化学后果是否也受到β 2缺乏的影响，评估了响应于Fc受体连接的LTB 4产生。与对照PMN相比，粘附于IC涂覆表面的β 2缺陷PMN的LTB 4产生显著降低。重要的是，由PMN用液相热聚集IgG刺激产生的LTB 4也需要β 2整联蛋白，表明该缺陷不是异常粘附的简单结果。相比之下，超氧化物的生产IC粘附PMN是相当的控制和β 2-缺乏PMN。胞浆内[Ca 2 +]i响应聚集IgG的初始升高也不受β 2整合素抑制的影响。这些数据表明，缺乏β 2整联蛋白不会抑制所有的FcR依赖性信号转导。最后，LTB 4的生产正常PMN粘附IC抑制抗体FcRII，但不FcRIII，表明FcRII连接所需的这种效果。这些数据共同确定了β 2整联蛋白在信号转导途径中的作用，该信号转导途径导致响应IC的持续粘附和LTB 4产生。由于β 2整联蛋白和FcRII都是这些作用所必需的，因此数据进一步表明这些受体在响应IC刺激产生PMN活化中的合作。
The beta 2 integrins (LFA-1, Mac-1, and p150,95) are critical for many adhesive functions of leukocytes. Although the binding of the IgG- opsonized particles occurs normally in the absence of beta 2 integrins, phagocytosis of IgG-opsonized particles by activated neutrophils (PMN) requires these integrins. This observation suggests a role for beta 2 integrins in phagocytosis subsequent to particle binding. To investigate the mechanism of involvement of beta 2 integrins in IgG- mediated functions, we examined the role of beta 2 integrins in adhesion to immune complex (IC)-coated surfaces. Initial adhesion and spreading on IC-coated surfaces were equivalent in control and beta 2- deficient phagocytes. However, both genetically beta 2-deficient PMN and PMN treated with the anti-beta 2 mAb IB4 subsequently detached from the IC-coated surfaces. To determine whether biochemical consequences of IgG activation were also affected by beta 2 deficiency, LTB4 production in response to Fc receptor ligation was assessed. LTB4 production by beta 2-deficient PMN adherent to IC-coated surfaces was markedly decreased in comparison with control PMN. Importantly, LTB4 production by PMN stimulated with fluid phase heat-aggregated IgG also required the beta 2 integrins, showing that the defect was not a simple consequence of abnormal adhesion. In contrast, superoxide production by IC-adherent PMN was equivalent in control and beta 2-deficient PMN. The initial rises in intracytoplasmic [Ca2+]i in response to aggregated IgG also were unaffected by inhibition of beta 2 integrins. These data show that lack of beta 2 integrins does not inhibit all FcR-dependent signal transduction. Finally, LTB4 production by normal PMN adherent to ICs was inhibited by antibodies to FcRII, but not FcRIII, showing that FcRII ligation was required for this effect. Together these data identify a role for the beta 2 integrins in a signal transduction pathway leading to sustained adhesion and LTB4 production in response to IC. Since both beta 2 integrins and FcRII are required for these effects, the data further suggest cooperation between these receptors in generating PMN activation in response to IC stimulation.