Editors' ChoiceInfectious Disease

CD39 to the Rescue

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Science Translational Medicine  01 Aug 2012:
Vol. 4, Issue 145, pp. 145ec137
DOI: 10.1126/scitranslmed.3004664

An individual may breathe in more than half a million bacteria every day. Yet despite this assault, our body’s defenses are usually up to the task of preventing illness. One critical first-line defense against potential invaders is the mucus that lines our airways, which traps bacteria and other particles from the air. Beating cilia then move the mucus out of the airway, preventing colonization and potential infection. Extracellular adenosine 5´-triphosphate (ATP) and adenosine in the lungs are important for mucociliary clearance of inhaled particles or pathogens. Adenosine is generated from ATP by the sequential action of two enzymes: CD39 and CD73. Increased CD39 expression has been reported in various organs during inflammation and tissue damage. The contribution of a chronic increase of surface CD39 activity to lung inflammation is unclear.

Theatre et al. generated a transgenic mouse model that overexpressed human CD39 (hCD39) in airway epithelia and characterized the response of these mice to a bacterial challenge. They found that increased expression and activity of hCD39 in the transgenic mice led to an increase in inflammatory cell recruitment, alveolar permeability, inflammatory cytokine production, and P2 receptor activity in the lungs after exposure to a bacterial toxin, LPS. P2 receptor activity is normally limited by receptor desensitization by released ATP. When these hCD39 transgenic mice were infected with Pseudomonas aeruginosa, similar results were found. An increase in leukocyte infiltration and cytokine production was observed in the lungs. In addition, the hCD39 transgenic mice were able to eliminate the bacteria better than were wild-type mice.

In summary, Theatre et al. provide in vivo evidence that extracellular ATP in the lungs contributes to an immune response by activation and recruitment of inflammatory cells, which facilitates bacterial clearance. Their mouse model constitutes a new tool to further investigate the role of ATP and adenosine in chronic lung infections or allergic diseases, as well as to evaluate the therapeutic potential of aerosolized P1 or P2 receptor agonists and antagonists for these diseases.

E. Theatre et al., Overexpression of CD39 in mouse airways promotes bacteria-induced inflammation. J. Immunol., 16 July 2012 (10.4049/jimmunol.1102600). [PubMed]

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