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Ca V 3.1 (α 1G ) Controls von Willebrand Factor Secretion in Pulmonary Microvascular Endothelial Cells.
Author(s) -
Zhou Chun,
Chen Hairu,
Daigle Jonathan A.,
van Mourik Jan A.,
Wu Songwei
Publication year - 2006
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.20.4.a747-d
Subject(s) - exocytosis , von willebrand factor , thrombin , secretion , microbiology and biotechnology , chemistry , endothelium , hemostasis , immunology , medicine , endocrinology , biology , platelet , biochemistry
Netherlands The release of von Willebrand factor (vWF) resulting from the exocytosis of Weibel‐Palade bodies (WPBs) contributes to hemostasis and inflammation. The exocytosis of WPBs stimulated by G q ‐linked inflammatory agonists ( e.g. thrombin) requires Ca 2+ entry from the extracellular space. We have previously demonstrated that pulmonary microvascular endothelial cells (PMVECs), but not pulmonary artery endothelial cells (PAECs), express a Ca V 3.1 T‐type Ca2+ channel that is activated by thrombin, and the activation of this channel induces a procoagulant endothelial phenotype. In the present study, we sought to assess the role of the Ca V 3.1 channel in WPB exocytosis and consequent vWF release. In PMVECs and PAECs transduced with a GFP‐tagged vWF chimera, we examined the real time dynamics and secretory process of the GFP‐containing vesicles, which closely resembled WPBs, in response to thrombin and a cAMP‐elevating agent, isoproterenol. While both thrombin and isoproterenol stimulated a rapid, progressive decrease in the number of GFP‐containing vesicles in the two cell types, only in PMVECs was the thrombin‐induced decrease in numbers of GFP‐containing vesicles nearly abolished by mibefradil (10 μM), the T‐type Ca 2+ channel blocker. Collectively, these data indicate that the exocytosis of WPBs in lung endothelial cells is regulated by two distinct pathways that are Ca 2+ ‐ or cAMP‐dependent. These results further support the hypothesis that activation of the T‐type Ca 2+ channel in PMVECs provides a unique [Ca 2+ ] i source important for the Gq‐linked agonist‐induced exocytosis of WPBs. Supported by HL074116