Thrombin enhances the barrier function of rat microvascular endothelium in a PAR-1-dependent manner

Troyanovsky, Boris; Alvarez, Diego F.; King, Judy; Schaphorst, Kane L.

doi:10.1152/ajplung.00107.2007

Cited by 24 publications

(16 citation statements)

References 47 publications

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“…Interestingly, endothelial responses to thrombin exhibit a segment-specific heterogeneity in the pulmonary circulation, e.g., barrier disruption in conduit vessels vs. barrier enhancement in alveolar capillaries (43). In the present study, we demonstrated that P-selectin surface expression is stimulated by thrombin in both extra-alveolar vessel and alveolar capillary endothelium.…”

Section: Discussionsupporting

confidence: 61%

α_1GT-type calcium channel selectively regulates P-selectin surface expression in pulmonary capillary endothelium

Zhou¹,

Chen²,

King³

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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Townsley MI, Shin HS, Wu S. ␣ 1G T-type calcium channel selectively regulates P-selectin surface expression in pulmonary capillary endothelium. Am J Physiol Lung Cell Mol Physiol 299: L86 -L97, 2010. First published April 30, 2010 doi:10.1152/ajplung.00331.2009.-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 ␣ 1G-subunit. Depolarization of endothelial plasma membrane via high K ϩ perfusion capable of eliciting cytosolic Ca 2ϩ transients also provoked P-selectin surface expression in alveolar capillaries that was abolished by T-type channel blockade or ␣ 1G knockout. Our findings reveal an intracellular WPb-independent Pselectin pool in pulmonary capillary endothelium, where the regulated P-selectin surface expression is triggered by Ca 2ϩ transients evoked through activation of the ␣ 1G T-type channel.

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Section: Discussionsupporting

confidence: 61%

α_1GT-type calcium channel selectively regulates P-selectin surface expression in pulmonary capillary endothelium

Zhou¹,

Chen²,

King³

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…As might be expected in this case, ligation of toll-like receptor 4 by LPS plays a key role in initiation of endothelial hyperpermeability in endotoxinmediated barrier injury (130). In addition, other upstream receptors have been shown to be involved in barrier regulation; thrombin increased EC permeability in EC monolayers (315) and increased macrovascular (but not microvascular) EC permeability in isolated, perfused rat lungs (636).…”

Section: Signals Leading To Initiation Of Barrier Disruptionmentioning

confidence: 62%

Lung Circulation

Suresh

Shimoda

2016

Comprehensive Physiology

104

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The circulation of the lung is unique both in volume and function. For example, it is the only organ with two circulations: the pulmonary circulation, the main function of which is gas exchange, and the bronchial circulation, a systemic vascular supply that provides oxygenated blood to the walls of the conducting airways, pulmonary arteries and veins. The pulmonary circulation accommodates the entire cardiac output, maintaining high blood flow at low intravascular arterial pressure. As compared with the systemic circulation, pulmonary arteries have thinner walls with much less vascular smooth muscle and a relative lack of basal tone. Factors controlling pulmonary blood flow include vascular structure, gravity, mechanical effects of breathing, and the influence of neural and humoral factors. Pulmonary vascular tone is also altered by hypoxia, which causes pulmonary vasoconstriction. If the hypoxic stimulus persists for a prolonged period, contraction is accompanied by remodeling of the vasculature, resulting in pulmonary hypertension. In addition, genetic and environmental factors can also confer susceptibility to development of pulmonary hypertension. Under normal conditions, the endothelium forms a tight barrier, actively regulating interstitial fluid homeostasis. Infection and inflammation compromise normal barrier homeostasis, resulting in increased permeability and edema formation. This article focuses on reviewing the basics of the lung circulation (pulmonary and bronchial), normal development and transition at birth and vasoregulation. Mechanisms contributing to pathological conditions in the pulmonary circulation, in particular when barrier function is disrupted and during development of pulmonary hypertension, will also be discussed.

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“…There have been attempts to measure changes in filtration coefficient in isolated lungs in response to thrombin perfusion [46,47,48]. However, the K F,C is expressed in relation to capillary pressure which therefore must stay constant during the measurement [49,50].…”

Section: Platelet-activating Factor (Paf)mentioning

confidence: 99%

Differential Regulation of Lung Endothelial Permeability in Vitro and in Situ

Uhlig

Yang

Waade

et al. 2014

Cell Physiol Biochem

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In the lungs, increased vascular permeability can lead to acute lung injury. Because vascular permeability is regulated primarily by endothelial cells, many researchers have studied endothelial cell monolayers in culture, in order to understand the pathomechanisms of pulmonary edema. Such studies are based on the assumption that endothelial cells in culture behave like endothelial cells in situ. Here we show that this assumption is largely unfounded. Cultured endothelial cells show profound differences compared to their physiological counterparts, including a dysregulated calcium homeostasis. They fail to reproduce the pulmonary responses to agents such as platelet-activating factor. In contrast, they respond in a Rho-kinase depend fashion to thrombin, LPS or TNF. This is a striking finding for three reasons: (i) in the lungs, none of these agents increases vascular permeability by a direct interaction with endothelial cells; (ii) The endothelial Rho-kinase pathway seems to play little role in the development of pulmonary edema; (iii) This response pattern is similar for many endothelial cells in culture irrespective of their origin, which is in contrast to the stark heterogeneity of endothelial cells in situ. It appears that most endothelial in culture tend to develop a similar phenotyp that is not representative of any of the known endothelial cells of the lungs. We conclude that at present cultured endothelial cells are not useful to study the pathomechanisms of pulmonary edema.

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Thrombin enhances the barrier function of rat microvascular endothelium in a PAR-1-dependent manner

Abstract: Troyanovsky B, Alvarez DF, King JA, Schaphorst KL. Thrombin enhances the barrier function of rat microvascular endothelium in a PAR-1-dependent manner.

Cited by 24 publications

References 47 publications

α_1GT-type calcium channel selectively regulates P-selectin surface expression in pulmonary capillary endothelium

α_1GT-type calcium channel selectively regulates P-selectin surface expression in pulmonary capillary endothelium

Lung Circulation

Differential Regulation of Lung Endothelial Permeability <b><i>in Vitro</i></b> and <b><i>in Situ</i></b>

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Thrombin enhances the barrier function of rat microvascular endothelium in a PAR-1-dependent manner

Abstract: Troyanovsky B, Alvarez DF, King JA, Schaphorst KL. Thrombin enhances the barrier function of rat microvascular endothelium in a PAR-1-dependent manner.

Cited by 24 publications

References 47 publications

α1GT-type calcium channel selectively regulates P-selectin surface expression in pulmonary capillary endothelium

α1GT-type calcium channel selectively regulates P-selectin surface expression in pulmonary capillary endothelium

Lung Circulation

Differential Regulation of Lung Endothelial Permeability <b><i>in Vitro</i></b> and <b><i>in Situ</i></b>

Contact Info

Product

Resources

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α_1GT-type calcium channel selectively regulates P-selectin surface expression in pulmonary capillary endothelium

α_1GT-type calcium channel selectively regulates P-selectin surface expression in pulmonary capillary endothelium