首页> 外文期刊>American Journal of Physiology >Alpha1G T-type calcium channel selectively regulates P-selectin surface expression in pulmonary capillary endothelium.
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Alpha1G T-type calcium channel selectively regulates P-selectin surface expression in pulmonary capillary endothelium.

机译:Alpha1G T型钙通道选择性调节肺毛细血管内皮细胞中P-选择素的表面表达。

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摘要

Regulated P-selectin surface expression provides a rapid measure for endothelial transition to a proinflammatory phenotype. In general, P-selectin surface expression results from Weibel-Palade body (WPb) exocytosis. Yet, it is unclear whether pulmonary capillary endothelium possesses WPbs or regulated P-selectin surface expression and, if so, how inflammatory stimuli initiate exocytosis. We used immunohistochemistry, immunofluorescence labeling, ultrastructural assessment, and an isolated perfused lung model to demonstrate that capillary endothelium lacks WPbs but possesses P-selectin. Thrombin stimulated P-selectin surface expression in both extra-alveolar vessel and alveolar capillary endothelium. Only in capillaries was the thrombin-stimulated P-selectin surface expression considerably mitigated by pharmacologic blockade of the T-type channel or genetic knockout of the T-type channel alpha(1G)-subunit. Depolarization of endothelial plasma membrane via high K(+) perfusion capable of eliciting cytosolic Ca(2+) transients also provoked P-selectin surface expression in alveolar capillaries that was abolished by T-type channel blockade or alpha(1G) knockout. Our findings reveal an intracellular WPb-independent P-selectin pool in pulmonary capillary endothelium, where the regulated P-selectin surface expression is triggered by Ca(2+) transients evoked through activation of the alpha(1G) T-type channel.
机译:调节的P-选择蛋白表面表达为内皮向促炎表型的转变提供了快速的方法。通常,P-选择蛋白表面表达是由韦伯-帕拉德氏体(WPb)胞吐作用产生的。然而,尚不清楚肺毛细血管内皮细胞是否具有WPbs或受调节的P-选择素表面表达,如果存在,还不清楚炎症刺激如何引发胞吐作用。我们使用免疫组化,免疫荧光标记,超微结构评估和孤立的肺灌注模型来证明毛细血管内皮缺乏WPbs,但拥有P-选择素。凝血酶刺激肺泡外血管和肺泡毛细血管内皮中的P-选择素表面表达。仅在毛细血管中,凝血酶刺激的P-选择素表面表达会通过药理性阻断T型通道或T型通道alpha(1G)-亚基的基因敲除而大大减轻。内皮细胞质膜通过高K(+)灌注能够引起胞质Ca(2+)瞬变去极化也引起了肺泡毛细血管中的P-选择素表面表达,该表达被T型通道阻断或alpha(1G)敲除所取消。我们的发现揭示了肺毛细血管内皮细胞中不依赖于WPb的P-选择素池,其中受调节的P-选择素表面表达是由激活α(1G)T型通道引起的Ca(2+)瞬变触发的。

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