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Evaluation of CD39 and CD73 ectoenzymes expressed in lymphocytes, monocytes and neutrophils of septic patients

Grant number: 15/21950-2
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2015
Effective date (End): October 31, 2016
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Reinaldo Salomão
Grantee:Luana de Queiroz Dourado
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

Abstract

Evaluation of CD39 and CD73 ectoenzymes expressed in lymphocytes, monocytes and neutrophils of septic patients. Sepsis is defined as a systemic infection triggered by an exacerbated inflammatory response resulting in severe damage to the host, which may lead to organ dysfunction. It is considered a public health problem and is currently the leading cause of death in intensive care units (ICU), making it a challenge to science. The lymphocytes, monocytes and neutrophils are cells of immune system, involved in controlling pathogenic infections. These cells express receptors on their surface that can decrease the inflammatory process.The CD39 (E-NTPDase) is a membrane protein that hydrolyzes a phosphate from ATP, converting it into ADP. This is also responsible for the hydrolysis of a phosphate ADP, reducing it to AMP. The CD73 (Ecto-5'-nucleotidase) is a glycoprotein which completes the cycle of degradation, hydrolyzing the phosphate AMP, reducing it to adenosine. These receptors are referred to as ectoenzymes responsible for degrading ATP, ADP and AMP in the extracellular environment. These molecules are released into the extracellular environment by pannexin channels, lysis, or cell damage, which triggers the inflammatory process. These receptors are considered the largest metabolizing ectoenzymes nucleotides through hydrolysis mechanism that may decrease inflammatory process. The role of these receptors is not clear in sepsis, although studies suggest that they can reduce the inflammatory response while decreasing bacterial proliferation. The objectives of this study are to evaluate the expression of CD39 and CD73 receptors in lymphocytes, monocytes and neutrophils by flow cytometry in whole fresh blood and quantify the ATP, ADP and AMP in the plasma of septic individuals by HPLC. The study will include 60 septic patients within 48 hours of diagnosis admitted to the São Paulo, Sírio-Libanês and Albert Einstein Hospitals. Thirty healthy subjects will be included as controls. The expression of surface receptor will be correlated with ATP, ADP, AMP and adenosine plasma levels of the individuals.