Evaluation of energy and oxidative metabolism in peripheral blood mononuclear cells (PBMC) from septic patients

• Grant number: 16/13855-2
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): December 01, 2016
• Effective date (End): November 30, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Reinaldo Salomão
• Grantee: Bianca Rodrigues Lima Ferreira
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 11/20401-4 - Sepsis: integrating basic research and clinical research II, AP.TEM
• Associated scholarship(s): 19/02224-0 - Metabolism in airway epithelium and immune cells during homeostasis and inflammation, BE.EP.DR

Abstract

Sepsis is the leading cause of death in ICU and can be defined as a dysregulated host response to infection, which causes organ dysfunction. Recent data indicate that both pro-inflammatory and anti-inflammatory responses take place simultaneously since the early stages of sepsis. And several studies have shown the importance of energy metabolism in regulation of immune response, which acts even in order to coordinate cell function and fate. Different cells of innate and adaptive responses, for instance, when activated switch their metabolism from oxidative phosphorylation to aerobic glycolysis, a phenomenon known as Warburg effect, that is regulated by HIF (hypoxia inducible transcription factor). Results obtained by our group have pointed to changes in cell metabolism and indicate modifications in protein expression of metabolic pathways in plasma of septic patients. Thus, the aim of this project is to analyze how mitochondrial function and cellular metabolism are altered in peripheral blood mononuclear cells (PBMC) of septic patients. We will perform proteomic analysis in PBMC samples of septic and healthy individuals, focusing on proteins related to cell metabolism; and validation will be done by western blotting assays. To check for metabolism transition to aerobic glycolysis, lactate and NAD + will be measured in these cells, and we will also analyze the expression of genes related to HIF by PCR array. This study will help in the comprehension of cellular events that regulate immunomodulation in sepsis, assisting in search for effective therapies and new diagnostic methods.