Increased NTPDase Activity in Lymphocytes during Experimental Sepsis

Claudia De Mello Bertoncheli,Jeandre Augusto Dos Santos Jaques,Kelly De Vargas Pinheiro,Sônia Cristina Almeida Luz,Cláudio Alberto Martins Leal,Viviane Do Carmo Gonçalves Souza,Jader Betsch Ruchel,Bruna Cipolatto Rocha,Maria Rosa Chitolina Schetinger,Daniela Bitencourt Rosa Leal,Carine Eloise Prestes Zimmermann,Daniel Roulim Stainki

doi:10.1100/2012/941906

Claudia De Mello Bertoncheli, Jeandre Augusto Dos Santos Jaques + Show 10 more

Open Access

https://doi.org/10.1100/2012/941906

Copy DOI

Abstract

We investigated in rats induced to sepsis the activity of ectonucleoside triphosphate diphosphohydrolase (NTPDase; CD39; E.C. 3.6.1.5), an enzyme involved in the modulation of immune responses. After 12 hours of surgery, lymphocytes were isolated from blood and NTPDase activity was determined. It was also performed the histology of kidney, liver, and lung. The results demonstrated an increase in the hydrolysis of adenosine-5′-triphosphate (ATP) (P < 0.01), but no changes regarding adenosine-5′-monophosphate (ADP) hydrolysis (P > 0.05). Histological analysis showed several morphological changes in the septic group, such as vascular congestion, necrosis, and infiltration of mononuclear cells. It is known that the intracellular milieu contains much more ATP nucleotides than the extracellular. In this context, the increased ATPasic activity was probably induced as a dynamic response to clean up the elevated ATP levels resulting from cellular death.

Highlights

Sepsis is characterized by an inflammatory reaction as a consequence of immune system response to bacterial infection [1, 2]
The results demonstrated an increase in the hydrolysis of adenosine-5 -triphosphate (ATP) (P < 0.01), but no changes regarding adenosine5 -monophosphate (ADP) hydrolysis (P > 0.05)
The statistical analysis demonstrated that animals from septic group had an increased ATP hydrolysis (P < 0.01) (Figure 1(a)) but did not show any statistical difference (P > 0.05) in regard to ADP hydrolysis (Figure 1(b))

Summary

Introduction

Sepsis is characterized by an inflammatory reaction as a consequence of immune system response to bacterial infection [1, 2]. The exacerbated activation of innate immune response is one of the main components involved in the physiopathology of sepsis, which can be identified by increased proinflammatory factors after infection [6]. The membrane bound enzyme ectonucleoside triphosphate diphosphohydrolase (NTPDase; CD39; E.C. 3.6.1.5) modulates adenine nucleotides level, which are fundamental to the modulation of immune responses [7]. The enzymes of this family are widely distributed in animal tissues and represent the main ectoenzyme expressed by endothelial cells and muscle cells of the circulatory system [8, 9]. It is known that extracellular ATP, for example, when in micromolar concentrations, can induce the formation of pores in the cell membranes, resulting in osmotic changes [11], and it can induce two antagonistic effects: cell

Objectives

Methods

Results

Conclusion