α 1G 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 Citations (Scopus)

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 α 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 α 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 α 1G T-type channel.

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

Fingerprint

T-Type Calcium Channels
P-Selectin
Vascular Endothelium
Lung
Weibel-Palade Bodies
Exocytosis
Thrombin
Fluorescent Antibody Technique
Perfusion
Immunohistochemistry
Cell Membrane

Keywords

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

ASJC Scopus subject areas

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

Cite this

α 1G T-type calcium channel selectively regulates P-selectin surface expression in pulmonary capillary endothelium . / Zhou, Chun; Chen, Hairu; King, Judy A.; Sellak, Hassan; Kuebler, Wolfgang M.; Yin, Jun; Townsley, Mary I.; Shin, Hee Sup; Wu, Songwei.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 299, No. 1, 01.07.2010.

Research output: Contribution to journalArticle

Zhou, Chun ; Chen, Hairu ; King, Judy A. ; Sellak, Hassan ; Kuebler, Wolfgang M. ; Yin, Jun ; Townsley, Mary I. ; Shin, Hee Sup ; Wu, Songwei. / α 1G T-type calcium channel selectively regulates P-selectin surface expression in pulmonary capillary endothelium In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2010 ; Vol. 299, No. 1.
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