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Stimulation of A2B adenosine receptors protects against trauma–hemorrhagic shock-induced lung injury

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Abstract

Inflammation is responsible for secondary organ failure after trauma and hemorrhagic shock (T/HS). Adenosine, acting through four G protein-coupled cell surface receptors, A1, A2A, A2B, and A3, exerts a number of tissue protective and anti-inflammatory effects. The goal of the present study was to test the effect of A2B adenosine receptor stimulation on T/HS-induced organ injury and inflammation in rats. Rats after T/HS were resuscitated with Ringer’s lactate containing the A2B receptor agonist BAY 60–6583 or its vehicle. We found that BAY 60–6583 decreased T/HS-induced lung permeability and plasma creatine kinase levels but failed to affect T/HS-induced lung neutrophil infiltration and IκBα expression and plasma alanine aminotransferase levels. Thus, we conclude that stimulation of A2B receptors protects against T/HS-induced lung and muscle injury.

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Acknowledgments

This work was supported by National Institutes of Health grants R01GM066189; USAMRMC grant log# 09065004 (contract W81XWH-10-1-1015); Hungarian Scientific Research Fund (OTKA) grant CK 78275 to GH; National Heart Institute Grants R01-HL0921, R01-DK083385, and R01-HL098294; and a grant by the Crohn’s and Colitis Foundation of America to HKE.

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Authors and Affiliations

  1. Department of Surgery, University of Medicine and Dentistry of New Jersey—New Jersey Medical School, 185 South Orange Avenue, University Heights, Newark, NJ, 07103, USA

    Balázs Koscsó, Alexey Trepakov, Balázs Csóka & György Haskó

  2. Mucosal Inflammation Program, Department of Anesthesiology, University of Colorado Medical School, Aurora, CO, USA

    Holger K. Eltzschig

  3. Department of Surgery, Morristown Medical Center, Morristown, NJ, USA

    Zoltán H. Németh

  4. Section on Oxidative Stress Tissue Injury, Laboratory of Physiological Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA

    Pál Pacher

  5. Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

    György Haskó

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  1. Balázs Koscsó
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  2. Alexey Trepakov
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Correspondence to György Haskó.

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Balázs Koscsó and Alexey Trepakov contributed equally to this work.

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Koscsó, B., Trepakov, A., Csóka, B. et al. Stimulation of A2B adenosine receptors protects against trauma–hemorrhagic shock-induced lung injury. Purinergic Signalling 9, 427–432 (2013). https://doi.org/10.1007/s11302-013-9362-7

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  • DOI: https://doi.org/10.1007/s11302-013-9362-7

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