scholarly journals Adenosine Receptor A1 Regulates Polymorphonuclear Cell Trafficking and Microvascular Permeability in Lipopolysaccharide-Induced Lung Injury

2010 ◽  
Vol 185 (7) ◽  
pp. 4374-4384 ◽  
Author(s):  
Kristian-Christos Ngamsri ◽  
Rosalyn Wagner ◽  
Irene Vollmer ◽  
Stefanie Stark ◽  
Jörg Reutershan
Keyword(s):  
Lung Injury ◽  
Adenosine Receptor ◽  
Microvascular Permeability ◽  
Cell Trafficking ◽  
Polymorphonuclear Cell ◽  
Adenosine Receptor A1

scholarly journals Adenosine receptor A2b on hematopoietic cells mediates LPS-induced migration of PMNs into the lung interstitium

2012 ◽  
Vol 303 (5) ◽  
pp. L425-L438 ◽  
Author(s):  
Franziska M. Konrad ◽  
Esther Witte ◽  
Irene Vollmer ◽  
Stefanie Stark ◽  
Jörg Reutershan
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Adenosine Receptor ◽  
Hematopoietic Cells ◽  
Microvascular Permeability ◽  
Critical Event ◽  
Cell Trafficking ◽  
Alveolar Space ◽  
Human Pmns

Uncontrolled transmigration of polymorphonuclear leukocytes (PMNs) into the different compartments of the lungs (intravascular, interstitial, alveolar) is a critical event in the early stage of acute lung injury and acute respiratory distress syndrome. Adenosine receptor A2b is highly expressed in the inflamed lungs and has been suggested to mediate cell trafficking. In a murine model of LPS-induced lung inflammation, we investigated the role of A2b on migration of PMNs into the different compartments of the lung. In A2b−/− mice, LPS-induced accumulation of PMNs was significantly higher in the interstitium, but not in the alveolar space. In addition, pulmonary clearance of PMNs was delayed in A2b−/− mice. Using chimeric mice, we identified A2b on hematopoietic cells as crucial for PMN migration. A2b did not affect the release of relevant chemokines into the alveolar space. LPS-induced microvascular permeability was under the control of A2b on both hematopoietic and nonhematopoietic cells. Activation of A2b on endothelial cells also reduced formation of LPS-induced stress fibers, highlighting its role for endothelial integrity. A specific A2b agonist (BAY 60–6583) was effective in decreasing PMN migration into the lung interstitium and microvascular permeability. In addition, in vitro transmigration of human PMNs through a layer of human endothelial or epithelial cells was A2b dependent. Activation of A2b on human PMNs reduced oxidative burst activity. Together, our results demonstrate anti-inflammatory effects of A2b on two major characteristics of acute lung injury, with a distinct role of hematopoietic A2b for cell trafficking and endothelial A2b for microvascular permeability.

Increased cardiac microvascular permeability and activation of cardiac endothelial nitric oxide synthase in high tidal volume ventilation-induced lung injury

2010 ◽  
Vol 4 (1) ◽  
pp. 27-36
Author(s):  
Ming-Jui Hung ◽  
Ming-Yow Hung ◽  
Wen-Jin Cherng ◽  
Li-Fu Li
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Lung Injury ◽  
Tidal Volume ◽  
Endothelial Nitric Oxide Synthase ◽  
Microvascular Permeability ◽  
Akt Phosphorylation ◽  
Enos Phosphorylation ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Abstract Background: Positive pressure ventilation with large tidal volumes has been shown to cause lung injury via the serine/threonine kinase-protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS)-pathways. However, the effects of high tidal volume (VT) ventilation on the heart are unclear. Objectives: Evaluate the effect of VT ventilation on the cardiac vascular permeability and intracellular Akt and eNOS signaling pathway. Methods: C57BL/6 and Akt knock-out (heterozygotes, +/−) mice were exposed to high VT (30 mL/kg) mechanical ventilation with room air for one and/or five hours. Results: High VT ventilation increased cardiac microvascular permeability and eNOS phosphorylation in a timedependent manner. Serum cardiac troponin I was increased after one hour of high VT ventilation. Cardiac Akt phosphorylation was accentuated after one hour and attenuated after five hours of high VT ventilation. Pharmacological inhibition of Akt with LY294002 and high VT ventilation of Akt+/− mice attenuated cardiac Akt phosphorylation, but not eNOS phosphorylation. Conclusion: High VT ventilation increased cardiac myocardial injury, microvascular permeability, and eNOS phosphorylation. Involvement of cardiac Akt in high VT ventilation was transient.

scholarly journals Imiquimod Suppresses Propagation of Herpes Simplex Virus 1 by Upregulation of Cystatin A via the Adenosine Receptor A1 Pathway

2012 ◽  
Vol 86 (19) ◽  
pp. 10338-10346 ◽  
Author(s):  
Y. Kan ◽  
T. Okabayashi ◽  
S.-i. Yokota ◽  
S. Yamamoto ◽  
N. Fujii ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Adenosine Receptor ◽  
Herpes Simplex Virus 1 ◽  
Cystatin A ◽  
Simplex Virus ◽  
Adenosine Receptor A1

Simvastatin attenuates acute lung injury by activation of A2B adenosine receptor

2021 ◽  
pp. 115460
Author(s):  
Hong-xia Li ◽  
Xiao-yan Liang ◽  
Jiong-he Wu ◽  
Ya-ping Yuan ◽  
Yue Gao ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Adenosine Receptor ◽  
A2b Adenosine Receptor

Colloidal gold particles as a new in vivo marker of early acute lung injury

2004 ◽  
Vol 287 (4) ◽  
pp. L867-L878 ◽  
Author(s):  
Kai Heckel ◽  
Rainer Kiefmann ◽  
Martina Dörger ◽  
Mechthild Stoeckelhuber ◽  
Alwin E. Goetz
Keyword(s):  
Electron Microscopy ◽  
Acute Lung Injury ◽  
Gas Exchange ◽  
Lung Injury ◽  
Colloidal Gold ◽  
Microvascular Permeability ◽  
Arterial Oxygen ◽  
Control Group ◽  
Gold Particles

Permeability of the endothelial barrier to large molecules plays a pivotal role in the manifestation of early acute lung injury. We present a novel and sensitive technique that brings microanatomical visualization and quantification of microvascular permeability in line. White New Zealand rabbits were anesthetized and ventilated mechanically. Rabbit serum albumin (RSA) was labeled with colloidal gold particles. We quantified macromolecular leakage of gold-labeled RSA and thickening of the gas exchange distance by electron microscopy, taking into account morphology of microvessels. The control group receiving a saline solution represented a normal gas exchange barrier without extravasation of gold-labeled albumin. Infusion of lipopolysaccharide (LPS) resulted in a significant displacement of gold-labeled albumin into pulmonary cells, the lung interstitium, and even the alveolar space. Correspondingly, intravital fluorescence microscopy and digital image analysis indicated thickening of width of alveolar septa. The findings were accompanied by a deterioration of alveolo-arterial oxygen difference, whereas wet/dry ratio and albumin concentration in the bronchoalveolar lavage fluid failed to detect that early stage of pulmonary edema. Inhibition of the nuclear enzyme poly(ADP-ribose) synthetase by 3-aminobenzamide prevented LPS-induced microvascular injury. To summarize: colloidal gold particles visualized by standard electron microscopy are a new and very sensitive in vivo marker of microvascular permeability in early acute lung injury. This technique enabling detailed microanatomical and quantitative pathophysiological characterization of edema formation can form the basis for evaluating novel treatment strategies against acute lung injury.

scholarly journals An indispensable role of TRPC6‐mediated Ca2+ entry in increasing lung microvascular permeability and acute lung injury

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Mohammad Tauseef ◽  
Vidisha Kini ◽  
Nebojsa Knezevic ◽  
Stephen Vogel ◽  
Asrar Malik ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Microvascular Permeability

scholarly journals Distinct Roles for the A2B Adenosine Receptor in Acute and Chronic Stages of Bleomycin-Induced Lung Injury

2010 ◽  
Vol 186 (2) ◽  
pp. 1097-1106 ◽  
Author(s):  
Yang Zhou ◽  
Daniel J. Schneider ◽  
Eva Morschl ◽  
Ling Song ◽  
Mesias Pedroza ◽  
...  
Keyword(s):  
Lung Injury ◽  
Adenosine Receptor ◽  
A2b Adenosine Receptor

Failure of therapy with 2,3-dihydroxybenzoic acid to modify the course of sepsis-induced lung injury

1990 ◽  
Vol 69 (5) ◽  
pp. 1893-1902 ◽  
Author(s):  
M. D. Sharpe ◽  
R. A. Mustard ◽  
R. R. Finley ◽  
F. S. Rutledge ◽  
W. J. Sibbald
Keyword(s):  
Lung Injury ◽  
Total Protein ◽  
Cecal Ligation ◽  
Microvascular Permeability ◽  
Vehicle Group ◽  
Radical Scavenger ◽  
Dihydroxybenzoic Acid ◽  
Protein Ratio ◽  
Protein Clearance ◽  
Pulmonary Arterial

Oxidant-induced injury of the pulmonary microvasculature reportedly contributes to an increase in microvascular permeability and pulmonary hypertension, both of which are principal features of acute lung injury (ALI). We tested the hypothesis that antioxidant therapy with 2,3-dihydroxybenzoic acid (DHB), initiated in awake sheep after the development of sepsis-induced ALI, would ameliorate the progression of these lesions. DHB has many actions that suggested to us the potential for demonstrating benefit in ALI complicating sepsis; it is a nontoxic hydroxyl-radical scavenger that also inhibits the cyclooxygenase pathway and acts as a weak iron chelator. In preliminary experiments, we demonstrated that pretreatment with DHB prevented an increase in mean pulmonary arterial pressure, plasma thromboxane A2, measured as its metabolite thromboxane B2, and lymph total protein clearance that otherwise followed an infusion of zymosan-activated plasma (ZAP) in sheep. In subsequent experiments, 12 additional sheep were rendered septic by cecal ligation and perforation. Twenty-four to 36 h after cecal ligation and perforation, an increase in lung microvascular permeability was confirmed, because pulmonary lymph flow had increased by 82% while the mean lymph-to-plasma total protein ratio was unchanged from baseline. At this point, six sheep were then treated with parenteral DHB and six with DHB vehicle for the subsequent 24 h. In contrast to the demonstrated benefit of DHB pretreatment in preventing ALI secondary to an infusion of ZAP, the progressive increase in lymph total protein clearance that complicated septic lung injury in the DHB vehicle group throughout this 24-h study period was not ameliorated in the DHB treatment group. However, DHB did prevent a modest increase in mean pulmonary arterial pressures that was demonstrated in the DHB vehicle group throughout this 24-h treatment period. Although pretreatment prevented ALI after a ZAP infusion, we conclude that DHB only incompletely modified disease progression when administered after the onset of sepsis-induced ALI because it ameliorated the pulmonary hypertensive response without concurrently modifying an increase in lung microvascular fluid flux.

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