Deletion of the adenosine A 2A receptor increases the survival rate in a mice model of polymicrobial sepsis

Purinergic signalling

article

Miguel Meriño¹  Sebastián San Martín³  Pedro Sandaña⁵  Kurt Herlitz¹  Claudio Aguayo⁴  Alejandro Godoy⁴  Pablo Torres-Vergara⁴  Marcelo Gonzalez⁴  Felipe Troncoso¹  Jesenia Acurio¹  Carlos Escudero¹ 

[1] Vascular Physiology Laboratory, Group of Investigation in Tumor Angiogenesis (GIANT), Department of Basic Sciences, Faculty of Sciences, University of Bío-Bío;Universidad Adventista de Chile;Biomedical Research Centre, School of Medicine, Universidad de Valparaíso;Group of Research and Innovation in Vascular Health (GRIVAS Health);Clinical Hospital Herminda Martín;Universidad Católica de la Santísima Concepción;Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción;Department of Urology, Roswell Park Comprehensive Cancer Center;Universidad San Sebastián;Departamento de Farmacia, Facultad de Farmacia, Universidad de Concepción;Laboratorio de Investigación Materno-Fetal (LIMaf), Department of Obstetrics and Gynecology, Faculty of Medicine, University of Concepción

关键词: Sepsis;    A2A receptor;    Adenosine;    Immune response;    Bacterial load;    Endothelial damage;   

DOI  :  10.1007/s11302-020-09719-w

学科分类：分子生物学，细胞生物学和基因

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY