scholarly journals Cigarette smoke alters lung vascular permeability and endothelial barrier function (2017 Grover Conference Series)

2018 ◽  
Vol 8 (3) ◽  
pp. 204589401879400 ◽  
Author(s):  
Sharon Rounds ◽  
Qing Lu
Keyword(s):  
Cigarette Smoking ◽  
Vascular Permeability ◽  
Cigarette Smoke ◽  
Focal Adhesion ◽  
Barrier Function ◽  
Distress Syndrome ◽  
The United States ◽  
Endothelial Barrier Function ◽  
Lung Vascular Permeability ◽  
Reactive Aldehyde

Smoking of tobacco products continues to be widespread, despite recent progress in decreasing use. Both in the United States and worldwide, cigarette smoking is a major cause of morbidity and mortality. Growing evidence indicates that acute respiratory distress syndrome (ARDS) is among the consequences of cigarette smoking. Based on the topic from the 2017 Grover Conference, we review evidence that cigarette smoking increases lung vascular permeability using both acute and longer exposures of mice to cigarette smoke (CS). We also review studies indicating that CS extract disrupts cultured lung endothelial cell barrier function through effects on focal adhesion contacts, adherens junctions, actin cytoskeleton, and microtubules. Among the potentially injurious components of CS, the reactive aldehyde, acrolein, similarly increases lung vascular permeability and disrupts barrier function. We speculate that inhibition of aldehyde-induced lung vascular permeability may prevent CS-induced lung injury.

scholarly journals The G protein βγ subunit mediates reannealing of adherens junctions to reverse endothelial permeability increase by thrombin

2009 ◽  
Vol 206 (12) ◽  
pp. 2761-2777 ◽  
Author(s):  
Nebojsa Knezevic ◽  
Mohammad Tauseef ◽  
Tracy Thennes ◽  
Dolly Mehta
Keyword(s):  
Vascular Permeability ◽  
Focal Adhesion ◽  
Inflammatory Mediator ◽  
Adherens Junctions ◽  
Endothelial Permeability ◽  
Endothelial Barrier ◽  
Dependent Manner ◽  
Permeability Increase ◽  
Lung Vascular Permeability

The inflammatory mediator thrombin proteolytically activates protease-activated receptor (PAR1) eliciting a transient, but reversible increase in vascular permeability. PAR1-induced dissociation of Gα subunit from heterotrimeric Gq and G12/G13 proteins is known to signal the increase in endothelial permeability. However, the role of released Gβγ is unknown. We now show that impairment of Gβγ function does not affect the permeability increase induced by PAR1, but prevents reannealing of adherens junctions (AJ), thereby persistently elevating endothelial permeability. We observed that in the naive endothelium Gβ1, the predominant Gβ isoform is sequestered by receptor for activated C kinase 1 (RACK1). Thrombin induced dissociation of Gβ1 from RACK1, resulting in Gβ1 interaction with Fyn and focal adhesion kinase (FAK) required for FAK activation. RACK1 depletion triggered Gβ1 activation of FAK and endothelial barrier recovery, whereas Fyn knockdown interrupted with Gβ1-induced barrier recovery indicating RACK1 negatively regulates Gβ1-Fyn signaling. Activated FAK associated with AJ and stimulated AJ reassembly in a Fyn-dependent manner. Fyn deletion prevented FAK activation and augmented lung vascular permeability increase induced by PAR1 agonist. Rescuing FAK activation in fyn−/− mice attenuated the rise in lung vascular permeability. Our results demonstrate that Gβ1-mediated Fyn activation integrates FAK with AJ, preventing persistent endothelial barrier leakiness.

scholarly journals A Protective Role of FAM13A in Human Airway Epithelial Cells Upon Exposure to Cigarette Smoke Extract

2021 ◽  
Vol 12 ◽  
Author(s):  
Qing Chen ◽  
Maaike de Vries ◽  
Kingsley Okechukwu Nwozor ◽  
Jacobien A. Noordhoek ◽  
Corry-Anke Brandsma ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cigarette Smoking ◽  
Cigarette Smoke ◽  
Airway Epithelium ◽  
Barrier Function ◽  
Cigarette Smoke Extract ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Copd Patients ◽  
Epithelial Resistance

BackgroundChronic Obstructive Pulmonary Disease (COPD) is a progressive lung disease characterized by chronic inflammation upon inhalation of noxious particles, e.g., cigarette smoke. FAM13A is one of the genes often found to be associated with COPD, however its function in the pathophysiology of COPD is incompletely understood. We studied its role in airway epithelial barrier integrity and cigarette smoke-induced epithelial responses.Materials and MethodsProtein level and localization of FAM13A was assessed with immunohistochemistry in lung tissue from COPD patients and non-COPD controls. In vitro, FAM13A expression was determined in the absence or presence of cigarette smoke extract (CSE) in primary airway epithelial cells (AECs) from COPD patients and controls by western blotting. FAM13A was overexpressed in cell line 16HBE14o- and its effect on barrier function was monitored real-time by electrical resistance. Expression of junctional protein E-cadherin and β-catenin was assessed by western blotting. The secretion of neutrophil attractant CXCL8 upon CSE exposure was measured by ELISA.ResultsFAM13A was strongly expressed in airway epithelium, but significantly weaker in airways of COPD patients compared to non-COPD controls. In COPD-derived AECs, but not those of controls, FAM13A was significantly downregulated by CSE. 16HBE14o- cells overexpressing FAM13A built up epithelial resistance significantly more rapidly, which was accompanied by higher E-cadherin expression and reduced CSE-induced CXCL8 levels.ConclusionOur data indicate that the expression of FAM13A is lower in airway epithelium of COPD patients compared to non-COPD controls. In addition, cigarette smoking selectively downregulates airway epithelial expression of FAM13A in COPD patients. This may have important consequences for the pathophysiology of COPD, as the more rapid build-up of epithelial resistance upon FAM13A overexpression suggests improved (re)constitution of barrier function. The reduced epithelial secretion of CXCL8 upon CSE-induced damage suggests that lower FAM13A expression upon cigarette smoking may facilitate epithelial-driven neutrophilia.

Comparison of the effect of cigarette smoke on mesenchymal stem cells and dental stem cells

2020 ◽  
Author(s):  
Brandon Nguyen ◽  
Tamer Alpagot ◽  
Heesoo Oh ◽  
David Ojcius ◽  
Nan Xiao
Keyword(s):  
United States ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Cigarette Smoking ◽  
Cigarette Smoke ◽  
The United States ◽  
Systemic Effects ◽  
Dental Stem Cells ◽  
The Impact

The persistent prevalence of cigarette smoking continues to contribute to preventable disease and death in the United States. Although much is known about the deleterious systemic effects of cigarette smoke and nicotine, some clinically relevant areas still remain unclear, such as the impact of cigarette smoke and nicotine on stem cells and the subsequent implications in regenerative medicine. This review focuses on recent studies on the effect of cigarette smoke and one of its deleterious components nicotine on mesenchymal stem cells, with an emphasis on dental stem cells.

scholarly journals Adenosine protected against pulmonary edema through transporter- and receptor A2-mediated endothelial barrier enhancement

2010 ◽  
Vol 298 (6) ◽  
pp. L755-L767 ◽  
Author(s):  
Qing Lu ◽  
Elizabeth O. Harrington ◽  
Julie Newton ◽  
Brian Casserly ◽  
Gregory Radin ◽  
...  
Keyword(s):  
Pulmonary Edema ◽  
Adenosine Deaminase ◽  
Focal Adhesion ◽  
Adenosine Receptor ◽  
Barrier Function ◽  
Endothelial Barrier ◽  
Gtpase Activity ◽  
Endothelial Barrier Function ◽  
Rac1 Gtpase

We have previously demonstrated that adenosine plus homocysteine enhanced endothelial basal barrier function and protected against agonist-induced barrier dysfunction in vitro through attenuation of RhoA activation by inhibition of isoprenylcysteine-O-carboxyl methyltransferase. In the current study, we tested the effect of elevated adenosine on pulmonary endothelial barrier function in vitro and in vivo. We noted that adenosine alone dose dependently enhanced endothelial barrier function. While adenosine receptor A1 or A3 antagonists were ineffective, an adenosine transporter inhibitor, NBTI, or a combination of DPMX and MRS1754, antagonists for adenosine receptors A2A and A2B, respectively, partially attenuated the barrier-enhancing effect of adenosine. Similarly, inhibition of both A2A and A2B receptors with siRNA also blunted the effect of adenosine on barrier function. Interestingly, inhibition of both transporters and A2A/A2B receptors completely abolished adenosine-induced endothelial barrier enhancement. The adenosine receptor A2A and A2B agonist, NECA, also significantly enhanced endothelial barrier function. These data suggest that both adenosine transporters and A2A and A2B receptors are necessary for exerting maximal effect of adenosine on barrier enhancement. We also found that adenosine enhanced Rac1 GTPase activity and overexpression of dominant negative Rac1 attenuated adenosine-induced increases in focal adhesion complexes. We further demonstrated that elevation of cellular adenosine by inhibition of adenosine deaminase with Pentostatin significantly enhanced endothelial basal barrier function, an effect that was also associated with enhanced Rac1 GTPase activity and with increased focal adhesion complexes and adherens junctions. Finally, using a non-inflammatory acute lung injury (ALI) model induced by α-naphthylthiourea, we found that administration of Pentostatin, which elevated lung adenosine level by 10-fold, not only attenuated the development of edema before ALI but also partially reversed edema after ALI. The data suggest that adenosine deaminase inhibition may be useful in treatment of pulmonary edema in settings of ALI.

Tyrosine phosphorylation of paxillin/pp125FAK and microvascular endothelial barrier function

1998 ◽  
Vol 275 (1) ◽  
pp. H84-H93 ◽  
Author(s):  
Yuan Yuan ◽  
F. Y. Meng ◽  
Q. Huang ◽  
James Hawker ◽  
H. Mac Wu
Keyword(s):  
Endothelial Cells ◽  
Tyrosine Phosphorylation ◽  
Focal Adhesion ◽  
Barrier Function ◽  
Tyrosine Phosphatase ◽  
Endothelial Barrier ◽  
Protein Tyrosine Phosphorylation ◽  
Endothelial Barrier Function ◽  
Adhesion Proteins ◽  
Protein Tyrosine

The transendothelial movement of solutes is a dynamic process controlled by a complex interaction between the cytoskeleton and adhesion proteins. The aim of this study was to examine whether protein tyrosine phosphorylation is involved in the regulation of endothelial barrier function. The apparent permeability coefficient of albumin ( P a) was measured in isolated and perfused coronary venules. Tyrosine phosphatase inhibitors, including phenylarsine oxide and sodium orthovanadate, dose and time dependently increased basal P a. Western blot analysis of cultured coronary venular endothelial cells revealed that inhibition of tyrosine phosphatase induced an increase in phosphotyrosine content in a number of proteins, including bands at 65–70 and 120–130 kDa, which were identified as paxillin and focal adhesion kinase (pp125FAK), respectively. The time course and dose responsiveness of protein tyrosine phosphorylation were tightly correlated with those of increases in P a. Furthermore, stimulation of endothelial cells with histamine or phorbol myristate acetate (PMA) enhanced tyrosine phosphorylation of paxillin and pp125FAK, which was blocked by the tyrosine kinase inhibitor damnacanthal. Correspondingly, the increases in venular permeability elicited by histamine and PMA were abolished in damnacanthal-treated venules. Taken together, the data suggest a possible involvement of protein tyrosine phosphorylation in the control of endothelial barrier function. Paxillin and its associated focal adhesion proteins may play a specific role in agonist-induced hyperpermeability responses in the endothelium of exchange vessels.

scholarly journals Neutrophil transmigration, focal adhesion kinase and endothelial barrier function

2012 ◽  
Vol 83 (1) ◽  
pp. 82-88 ◽  
Author(s):  
Sarah Y. Yuan ◽  
Qiang Shen ◽  
Robert R. Rigor ◽  
Mack H. Wu
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Barrier Function ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function
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