Purinergic Signalling

, Volume 9, Issue 3, pp 325–336 | Cite as

Anti-inflammatory effects of inosine in allergic lung inflammation in mice: evidence for the participation of adenosine A2A and A3 receptors

  • Fernanda da Rocha Lapa
  • Ana Paula Ligeiro de Oliveira
  • Beatriz Golega Accetturi
  • Isabelli de Oliveira Martins
  • Helory Vanni Domingos
  • Daniela de Almeida Cabrini
  • Wothan Tavares de Lima
  • Adair Roberto Soares Santos
Original Article

Abstract

Inosine, a naturally occurring purine formed from the breakdown of adenosine, is associated with immunoregulatory effects. Evidence shows that inosine modulates lung inflammation and regulates cytokine generation. However, its role in controlling allergen-induced lung inflammation has yet to be identified. In this study, we aimed to investigate the role of inosine and adenosine receptors in a murine model of lung allergy induced by ovalbumin (OVA). Intraperitoneal administration of inosine (0.001–10 mg/kg, 30 min before OVA challenge) significantly reduced the number of leukocytes, macrophages, lymphocytes and eosinophils recovered in the bronchoalveolar lavage fluid of sensitized mice compared with controls. Interestingly, our results showed that pre-treatment with the selective A2A receptor antagonist (ZM241385), but not with the selective A2B receptor antagonist (alloxazine), reduced the inhibitory effects of inosine against macrophage count, suggesting that A2A receptors mediate monocyte recruitment into the lungs. In addition, the pre-treatment of mice with selective A3 antagonist (MRS3777) also prevented inosine effects against macrophages, lymphocytes and eosinophils. Histological analysis confirmed the effects of inosine and A2A adenosine receptors on cell recruitment and demonstrated that the treatment with ZM241385 and alloxazine reverted inosine effects against mast cell migration into the lungs. Accordingly, the treatment with inosine reduced lung elastance, an effect related to A2 receptors. Moreover, inosine reduced the levels of Th2-cytokines, interleukin-4 and interleukin-5, an effect that was not reversed by A2A or A2B selective antagonists. Our data show that inosine acting on A2A or A3 adenosine receptors can regulate OVA-induced allergic lung inflammation and also implicate inosine as an endogenous modulator of inflammatory processes observed in the lungs of asthmatic patients.

Keywords

Inosine Adenosine receptors Allergy Ovalbumin 

Notes

Acknowledgments

This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC), Programa de Reestruturação e Expansão das Universidades Federais (REUNI); Programa Nacional de Cooperação Acadêmica (PROCAD) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).

Conflicts of interest

None.

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Fernanda da Rocha Lapa
    • 1
    • 5
  • Ana Paula Ligeiro de Oliveira
    • 2
  • Beatriz Golega Accetturi
    • 3
  • Isabelli de Oliveira Martins
    • 3
  • Helory Vanni Domingos
    • 3
  • Daniela de Almeida Cabrini
    • 1
  • Wothan Tavares de Lima
    • 3
  • Adair Roberto Soares Santos
    • 4
  1. 1.Department of Pharmacology, Center of Biological SciencesFederal University of ParanáCuritibaBrazil
  2. 2.Department of Health SciencesUniversidade Nove de JulhoSão PauloBrazil
  3. 3.Department of Pharmacology, Biomedical Sciences InstituteUniversity of São PauloSão PauloBrazil
  4. 4.Department of Physiological SciencesFederal University of Santa CatarinaFlorianópolisBrazil
  5. 5.Department of Pharmacology, Center of Biological SciencesFederal University of Santa CatarinaFlorianópolisBrazil

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