Abstract
Background:
Adenosine levels are regulated by ecto-5'-nucleotidase/CD73 and adenosine deaminase (ADA). Adenosine regulates endothelial permeability and anti-inflammatory responses via adenosine receptors. Here, the adenosine receptors and purine-converting enzymes were studied during postnatal development and inflammation.
Methods:
Newborn, 1-, 10-, 14-d-old and adult C57BL/6 mice were challenged intraperitoneally (i.p.) with lipopolysaccharide (LPS) for 6 h. The inflammatory response was evaluated by histochemistry. Expression levels of adenosine receptors (A1, A2A, A2B, and A3), CD73, and ADA were measured by quantitative reverse transcription polymerase chain reaction. A1 was studied by immunohistochemistry, and enzyme activities were analyzed by thin-layer chromatography.
Results:
LPS caused respiratory distress in newborns within 24 h. LPS induced neutrophils at the basal stage and alveolar congestion. Low activity and expression of CD73 increased after birth. Expression of ADA after LPS increased 16-fold in adults and 2-fold in newborns (P < 0.05). A1 expression was high in newborns and increased after LPS (P < 0.05). A1 was localized to endothelial membranes. A2A decreased after LPS in newborns and increased in adults (P < 0.05). The expression of A3 increased in newborns and adults after LPS.
Conclusion:
Low pulmonary CD73 expression, LPS-induced suppression of A2A, LPS-induced increase of A1 expression, and severe respiratory distress were distinguishing responses in the newborns from those in the adults.
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Acknowledgements
We thank Maarit Haarala, Riitta Vuento, Sari Mäki, and Erja Tomperi for technical assistance.
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Metsola, J., Maksimow, M., Ojaniemi, M. et al. Postnatal development and LPS responsiveness of pulmonary adenosine receptor expression and of adenosine-metabolizing enzymes in mice. Pediatr Res 76, 515–521 (2014). https://doi.org/10.1038/pr.2014.132
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DOI: https://doi.org/10.1038/pr.2014.132
