Deletion of the adenosine A 2A receptor increases the survival rate in a mice model of polymicrobial sepsis
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ORIGINAL ARTICLE
Deletion of the adenosine A2A receptor increases the survival rate in a mice model of polymicrobial sepsis Miguel Meriño 1,2 & Sebastián San Martín 3,4 & Pedro Sandaña 5,6 & Kurt Herlitz 1 & Claudio Aguayo 4,7 & Alejandro Godoy 4,8,9 & Pablo Torres-Vergara 4,10 & Marcelo Gonzalez 4,11 & Felipe Troncoso 1 & Jesenia Acurio 1,4 & Carlos Escudero 1,4 Received: 30 May 2020 / Accepted: 28 July 2020 # Springer Nature B.V. 2020
Abstract We aim to investigate the role of A2A receptor in peritonitis-related sepsis by injection of a fecal solution (FS) as a model of polymicrobial infection. C57/black J6 wild-type (WT) and A2A-deficient mice (A2AKO) were exposed to sepsis induced by intraperitoneal injection of a FS (FS-induced peritonitis) or instead was injected with saline buffer (Sham). Survival rate and sepsis score were measured up to 48 h. The presence of bacteria in tissue homogenates was analyzed. Telemetry and speckle laser Doppler were used for systemic blood pressure and peripheral blood perfusion analysis, respectively. Histological analysis and identification of active caspase 3 were performed in selected organs, including the liver. The survival rate of A2AKO mice exposed to FS-induced peritonitis was significantly higher, and the sepsis score was lower than their respective WT counterpart. Injection of FS increases (50 to 150 folds) the number of colonies forming units in the liver, kidney, blood, and lung in WT mice, while these effects were significantly attenuated in A2AKO mice exposed to FS-induced peritonitis. A significant reduction in both systolic and diastolic blood pressure, as well as in the peripheral perfusion was observed in WT and A2AKO mice exposed to FS-induced peritonitis. Although, these last effects were significantly attenuated in A2AKO mice. Histological analysis showed a large perivascular infiltration of polymorphonuclear in the liver of WT and A2AKO mice exposed to FS-induced peritonitis, but again, this effect was attenuated in A2AKO mice. Finally, high expression of active caspase 3 was found only in the liver of WT mice exposed to FS-induced peritonitis. The absence of the A2A receptor increases the survival rate in mice exposed to polymicrobial sepsis. This outcome was associated with both hemodynamic compensation and enhanced anti-bacterial response. Keywords Sepsis . A2A receptor . Adenosine . Immune response . Bacterial load . Endothelial damage
Abbreviations A2A A2A adenosine receptor
ADO eNOS
* Carlos Escudero [email protected]
6
Universidad Católica de la Santísima Concepción, Concepción, Chile
7
Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile
8
Present address: Facultad de Ciencias de la Salud, Universidad Adventista de Chile, Chillan, Chile
Department of Urology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
9
Biomedical Research Centre, School of Medicine, Universidad de Valparaíso, Valparaíso, Chile
Centro de Biología Celular y Biomedicina (CEBICEM), U
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