Adenosine and inflammation: CD39 and CD73 are critical mediators in LPS-induced PMN trafficking into the lungs

Reutershan J, Vollmer I, Stark S, Wagner R, Ngamsri KC, Eltzschig HK (2009)


Publication Type: Journal article

Publication year: 2009

Journal

Book Volume: 23

Pages Range: 473-482

Journal Issue: 2

DOI: 10.1096/fj.08-119701

Abstract

Extracellular adenosine has been implicated as anti-inflammatory signaling molecule during acute lung injury (ALI). The main source of extracellular adenosine stems from a coordinated two-step enzymatic conversion of precursor nucleotides via the ectoapyrase (CD39) and the ecto-5′-nucleotidase (CD73). In the present study, we hypothesized a critical role of CD39 and CD73 in mediating pulmonary neutrophil (PMN) transmigration during lipopolysaccharide (LPS)-induced lung injury. Initial studies revealed that pulmonary CD39 and CD73 transcript levels were elevated following LPS exposure in vivo. Moreover, LPS-induced accumulation of PMN into the lungs was enhanced in cd39 -/- or cd73-/- mice, particularly into the interstitial and intra-alveolar compartment. Such increases in PMN trafficking were accompanied by corresponding changes in alveolar-capillary leakage. Similarly, inhibition of extracellular nucleotide phosphohydrolysis with the nonspecific ecto-nucleoside-triphosphate-diphosphohydrolases inhibitor POM-1 confirmed increased pulmonary PMN accumulation in wild-type, but not in gene-targeted mice for cd39 or cd73. Finally, treatment with apyrase or nucleotidase was associated with attenuated pulmonary neutrophil accumulation and pulmonary edema during LPS-induced lung injury. Taken together, these data reveal a previously unrecognized role for CD39 and CD73 in attenuating PMN trafficking into the lungs during LPS-induced lung injury and suggest treatment with their soluble compounds as a therapeutic strategy. © FASEB.

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APA:

Reutershan, J., Vollmer, I., Stark, S., Wagner, R., Ngamsri, K.-C., & Eltzschig, H.K. (2009). Adenosine and inflammation: CD39 and CD73 are critical mediators in LPS-induced PMN trafficking into the lungs. The FASEB Journal, 23(2), 473-482. https://dx.doi.org/10.1096/fj.08-119701

MLA:

Reutershan, Joerg, et al. "Adenosine and inflammation: CD39 and CD73 are critical mediators in LPS-induced PMN trafficking into the lungs." The FASEB Journal 23.2 (2009): 473-482.

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