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

• Grant number: 16/13855-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2016
• End date: September 30, 2021
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Reinaldo Salomão
• Grantee: Bianca Rodrigues Lima Ferreira
• Host 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.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERREIRA, BIANCA LIMA; SOUSA, MONICA BRAGANCA; LEITE, GIUSEPPE GIANINI FIGUEIREDO; BRUNIALTI, MILENA KARINA COLO; NISHIDUKA, ERIKA SAYURI; TASHIMA, ALEXANDRE KEIJI; VAN DER POLL, TOM; SALOMAO, REINALDO. Glucose metabolism is upregulated in the mononuclear cell proteome during sepsis and supports endotoxin-tolerant cell function. FRONTIERS IN IMMUNOLOGY, v. 13, p. 10-pg., 2022-11-18. (16/13855-2, 20/05077-5, 17/21052-0, 19/20532-3)

FERREIRA, BIANCA LIMA; FIGUEIREDO LEITE, GIUSEPPE GIANINI; COLO BRUNIALTI, MILENA KARINA; ASSUNCAO, MURILLO; PONTES AZEVEDO, LUCIANO CESAR; FREITAS, FLAVIO; SALOMAO, REINALDO. HIF-1 alpha and Hypoxia Responsive Genes are Differentially Expressed in Leukocytes From Survivors and Non-Survivors Patients During Clinical Sepsis. Shock, v. 56, n. 1, p. 80-91, JUL 2021. (17/21052-0, 16/13855-2)

FIGUEIREDO LEITE, GIUSEPPE GIANINI; FERREIRA, BIANCA LIMA; TASHIMA, ALEXANDRE KEIJI; NISHIDUKA, ERIKA SAYURI; CUNHA-NETO, EDECIO; COLO BRUNIALTI, MILENA KARINA; ASSUNCAO, MURILLO; PONTES AZEVEDO, LUCIANO CESAR; FREITAS, FLAVIO; VAN DER POLL, TOM; et al. Combined Transcriptome and Proteome Leukocyte's Profiling Reveals Up-Regulated Module of Genes/Proteins Related to Low Density Neutrophils and Impaired Transcription and Translation Processes in Clinical Sepsis. FRONTIERS IN IMMUNOLOGY, v. 12, SEP 10 2021. (19/20532-3, 17/21052-0, 16/13855-2)