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A distinct subcellular pool and an α 1G T‐type Ca 2+ channel regulated surface expression of P‐selectin in pulmonary capillary endothelium
Author(s) -
Zhou Chun,
Chen Hairu,
King Judy A.,
Sellak Hassan,
Kuebler Wolfgang M.,
Yin Jun,
Shin HeeSup,
Townsley Mary I.,
Wu Songwei
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.964.13
Subject(s) - endothelium , exocytosis , chemistry , microbiology and biotechnology , depolarization , p selectin , thrombin , biophysics , endothelial stem cell , platelet , biology , endocrinology , immunology , biochemistry , platelet activation , membrane , in vitro
Regulated P‐selectin surface expression provides a rapid measure of endothelial transition to a pro‐inflammatory 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. We used immunohistochemistry, immunofluorescence, 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 capillary endothelium. Only in capillaries was the thrombin‐stimulated P‐selectin surface expression markedly reduced by pharmacological inhibition of T‐type Ca 2+ channels, or by genetically eliminating T‐type channel α 1G ‐subunits. T‐type channel‐mediated cytosolic Ca 2+ transients were detected by real‐time imaging of fura‐2‐loaded capillary endothelium following plasma membrane depolarization via high K + perfusion. Depolarization also induced P‐selectin surface expression in capillary endothelium, which was abolished by T‐type channel blockade or eliminating α 1G ‐subunits. Collectively, these findings indicate that, in capillary endothelium, subcellular P‐selectin is WPB‐independent, and its regulated surface expression is driven by mechanism(s) distinct from WPB exocytosis; namely, Ca 2+ entry through the α 1G T‐type channel controls the regulated P‐selectin surface expression in capillary endothelium.