Evaluation of ATP-P2X7 axis during experimental asthma

Author(s)

Bruna de Gois Macêdo

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2021-01-29

Examining board members

Maria Regina D'Imperio Lima; Luciana Santos Cardoso; Ricardo Wesley Alberca Custodio; Momtchilo Russo

• Advisor: Maria Regina D'Imperio Lima

Abstract

Asthma is one of the most non-infectious widespread diseases in the world, with more than 339 million people living with the disease. Asthma-related symptoms include hardness to breath, excessive mucus production, coughing and wheezing. These symptoms are closely related to the immune responses promoted through the trigger generated by the allergen. In experimental asthma, extracellular ATP and P2X play an important role during the development of the disease, and these molecules seem to contribute to the regulation of antibody production during inflammatory processes. In this study we investigated the role of signaling through the ATP-P2X7 axis during the development of experimental asthma. It was observed a critical role of signaling through the P2X7 receptor for the development of eosinophilic infiltrate, but not for production of IgE antibodies during experimental asthma. P2rx7-/- mice showed lower number of CD4&#43CD44&#43 cells localized in the lung parenchyma compared to C57BL/6 mice during experimental asthma, as well as, these mice have CD4&#43CD44&#43GATA3&#43 cell infiltration similar to non-immunized mice, even upon immunization. In addition, mediastinal lymph node of immunized P2rx7-/- mice presented lower number of cells compared to that of C57BL/6 mice. We also characterized the role of ATP at high concentrations (1mM, 4.5mM and 50mM) during intranasal challenges, demonstrating the regulation through these molecules in the recruitment of eosinophils and production of IgE antibodies, probably through signaling by the P2X7 receptor, with increased production of IL-4 and no changes in CD4&#43CD44&#43GATA3&#43 cells. This study contributes to the understanding of how the signs of damage affect the development of asthma in experimental models, highlighting the P2X7 receptor as a potential therapeutic target related to asthmatic lung disease. (AU)

• FAPESP's process: 18/18664-6 - Evaluation of extracellular ATP and P2X7 receptor in t CD4+ lymphocytes modulation during pulmonary inflammation
• Grantee: Bruna de Gois Macêdo
• Support Opportunities: Scholarships in Brazil - Master