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Adenosine receptor A 2b on hematopoietic cells mediates LPS-induced migration of PMNs into the lung interstitium

Konrad FM, Witte E, Vollmer I, Stark S, Reutershan J (2012)

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Publication Type: Journal article

Publication year: 2012

Journal

Book Volume: 303

Pages Range: L425-L438

Journal Issue: 5

DOI: 10.1152/ajplung.00387.2011

Abstract

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 A 2b 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 A 2b on migration of PMNs into the different compartments of the lung. In A 2b ^-/- 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 A 2b ^-/- mice. Using chimeric mice, we identified A 2b on hematopoietic cells as crucial for PMN migration. A 2b did not affect the release of relevant chemokines into the alveolar space. LPS-induced microvascular permeability was under the control of A 2b on both hematopoietic and nonhematopoietic cells. Activation of A 2b on endothelial cells also reduced formation of LPS-induced stress fibers, highlighting its role for endothelial integrity. A specific A 2b 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 A 2b dependent. Activation of A 2b on human PMNs reduced oxidative burst activity. Together, our results demonstrate anti-inflammatory effects of A 2b on two major characteristics of acute lung injury, with a distinct role of hematopoietic A 2b for cell trafficking and endothelial A 2b for microvascular permeability. © 2012 the American Physiological Society.

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APA:

Konrad, F.M., Witte, E., Vollmer, I., Stark, S., & Reutershan, J. (2012). Adenosine receptor A 2b on hematopoietic cells mediates LPS-induced migration of PMNs into the lung interstitium. American Journal of Physiology-Lung Cellular and Molecular Physiology, 303(5), L425-L438. https://dx.doi.org/10.1152/ajplung.00387.2011

MLA:

Konrad, Franziska M., et al. "Adenosine receptor A 2b on hematopoietic cells mediates LPS-induced migration of PMNs into the lung interstitium." American Journal of Physiology-Lung Cellular and Molecular Physiology 303.5 (2012): L425-L438.

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