| First Author | Reutershan J | Year | 2009 |
| Journal | FASEB J | Volume | 23 |
| Issue | 2 | Pages | 473-82 |
| PubMed ID | 18838482 | Mgi Jnum | J:146027 |
| Mgi Id | MGI:3836524 | Doi | 10.1096/fj.08-119701 |
| Citation | Reutershan J, et al. (2009) Adenosine and inflammation: CD39 and CD73 are critical mediators in LPS-induced PMN trafficking into the lungs. FASEB J 23(2):473-82 |
| abstractText | 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 ecto-apyrase (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. |
