α1G T-type calcium channel selectively regulates P-selectin surface expression in pulmonary capillary endothelium

Chun Zhou, Hairu Chen, Judy A. King, Hassan Sellak, Wolfgang M. Kuebler, Jun Yin, Mary I. Townsley, Hee Sup Shin, Songwei Wu

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

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 α1G-subunit. Depolarization of endothelial plasma membrane via high K+ perfusion capable of eliciting cytosolic Ca2+ transients also provoked P-selectin surface expression in alveolar capillaries that was abolished by T-type channel blockade or α1G 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 Ca2+ transients evoked through activation of the α1G T-type channel.

Original languageEnglish (US)
Pages (from-to)L86-L97
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume299
Issue number1
DOIs
StatePublished - Jul 1 2010

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Keywords

  • Inflammation
  • Thrombin
  • Von Willebrand factor
  • Weibel-Palade body

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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