Participation of platelets in obesity-induced exacerbation of allergic airway disease

• Grant number: 22/03265-4
• Support type: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): September 30, 2022
• Effective date (End): September 29, 2023
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal researcher: Silvana Auxiliadora Bordin da Silva
• Grantee: Amanda Santos Cavalcante
• Supervisor abroad: Clive Peter Page
• Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Research place: King's College London, England
• Associated to the scholarship: 21/06444-4 - Changes in maternal gut microbiota induced by fructose consumption during pregnancy: implications for the inflammatory allergic airway response in the offspring, BP.DR

Abstract

The inflammatory response of allergic asthma is classically recognized as a predominantly TH2 activation that leads to IgE production and eosinophil development and infiltration in the lung parenchyma. Platelets also play a pivotal role in the inflammatory as evidenced by studies in which platelet depletion by reduced leukocyte accumulation in tissues in response to specific allergen exposure. Other studies have also shown platelet activation accompanying allergen-induced bronchoconstriction in asthmatic patients. We and others have demonstrated that obese mice subjected to experimental asthma display increased lung eosinophil infiltration in the lung parenchyma and in the broncoalveolar lavage (BAL) along with increased TH2 cytokines secretion. Besides the stated above, it is still unknown if platelet-induced leukocyte migration into the lung is significantly altered by obesity in allergic mice. In this project we will determine if platelets play a role in the exacerbation of allergic inflammation of obese mice subjected to the OVA model of allergic airway disease (AAD). Mice will be made obese by the use of high fat diet (HFD). Allergic asthma will be induced with the protocol of ovalbumin (OVA). Samples of BAL and lung will be used to attest the exacerbation of AAD. Peripheral leukocytes and platelets will be used to assess platelet-leukocytes chemotaxis and platelet-leukocyte interaction using flow cytometry. Platelet infiltration into the lung parenchyma will be evaluated by CD41 immunohistochemistry. We will also perform a protocol in which obese mice will be subjected to platelet depletion before induction of AAD with OVA. This protocol will be used to clarify if platelets are necessary for the exacerbation of AAD in obese mice. (AU)