CD16b associates with high-density, detergent-resistant membranes in human neutrophils
CD16b associates with high-density, detergent-resistant membranes in human neutrophils
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DOI：
10.1042/bj20050129
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发表时间：
2006-01-01
影响因子：
4.1
通讯作者：
Naccache, PH
中科院分区：
文献类型：
--
作者：
Fernandes, MJG;Rollet-Labelle, E;Naccache, PH
CD 16 b的独特之处在于它是通过GPI（糖基磷脂酰肌醇）锚与质膜连接的唯一Fc受体。GPI锚定蛋白通常优先定位于富含鞘脂和胆固醇的DRM（抗洗涤剂膜），并在信号转导中起重要作用。尽管已经深入研究了对CD 16 b接合的反应，但DRM完整性对CD 16 b信号传导的重要性尚未在人中性粒细胞中表征。我们提供的直接证据表明，CD 16 b组成分区与低密度和高密度DRM。此外，在CD 16 b接合后，在高密度DRM中观察到受体量的显著增加。与CD 16 b类似，CD 11b也存在于低密度和高密度DRM中。与CD 16 b相反，DRMs中CD 11b的分配不会响应于CD 16 b接合而改变。我们还提供了证据表明Syk在CD 16 b信号传导中的作用及其在静息和活化的PMN（多形核中性粒细胞）中对DRM的分配。此外，DRM破坏剂，如制霉菌素和甲基-β-环糊精，改变细胞对CD 16 b受体连接的反应。值得注意的是，观察到CD 16 b接合后细胞内Ca 2+的动员和细胞内底物的酪氨酸磷酸化显著增加。总之，本研究的结果提供了证据表明，高密度DRM在人类中性粒细胞中的CD 16 b信号传导中发挥作用。
CD16b is unique in that it is the only Fc receptor linked to the plasma membrane by a GPI (glycosylphosphatidylinositol) anchor. GPI-anchored proteins often preferentially localize to DRMs (detergent-resistant membranes) that are rich in sphingo-lipids and cholesterol and play an important role in signal transduction. Even though the responses to CD16b engagement have been intensively investigated, the importance of DRM integrity for CD16b signalling has not been characterized in human neutrophils. We provide direct evidence that CD16b constitutively partitions with both low- and high-density DRMs. Moreover, upon CD16b engagement, a significant increase in the amount of the receptor is observed in high-density DRMs. Similarly to CD16b, CD11b also resides in low- and high-density DRMs. In contrast with CD16b, the partitioning of CD11b in DRMs does not change in response to CD16b engagement. We also provide evidence for the implication of Syk in CD16b signalling and its partitioning to DRMs in resting and activated PMNs (polymorphonuclear neutrophils). Additionally, DRM-disrupting agents, such as nystatin and methyl-beta-cyclodextrin, alter cellular responses to CD16b receptor ligation. Notably, a significant increase in the mobilization of intracellular Ca2+ and in tyrosine phosphorylation of intracellular substrates after CD16b engagement is observed. Altogether, the results of this study provide evidence that high-density DRMs play a role in CD16b signalling in human neutrophils.