Deletion of the adenosine A2A receptor increases the survival rate in a mice model of polymicrobial sepsis

Meriño, Miguel; Martín, Sebastián San; Sandaña, Pedro; Herlitz, Kurt; Aguayo, Claudio; Godoy, Alejandro; Torres-Vergara, Pablo; González, Marcelo; Troncoso, Felipe; Acurio, Jesenia; Escudero, Carlos

doi:10.1007/s11302-020-09719-w

Cited by 7 publications

(11 citation statements)

References 58 publications

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“…Tissue perfusion analysis was performed using the Pericam ® PSI-HR system (Perimed Ltd., Stockholm, Sweden), as previously reported by our group [ 38 , 39 ], with some minor changes. The instrument uses an invisible near-infra-red laser to measure blood perfusion.…”

Section: Methodsmentioning

confidence: 99%

The GPI-Anchored Protein Thy-1/CD90 Promotes Wound Healing upon Injury to the Skin by Enhancing Skin Perfusion

Pérez

León

López

et al. 2022

IJMS

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Wound healing is a highly regulated multi-step process that involves a plethora of signals. Blood perfusion is crucial in wound healing and abnormalities in the formation of new blood vessels define the outcome of the wound healing process. Thy-1 has been implicated in angiogenesis and silencing of the Thy-1 gene retards the wound healing process. However, the role of Thy-1 in blood perfusion during wound closure remains unclear. We proposed that Thy-1 regulates vascular perfusion, affecting the healing rate in mouse skin. We analyzed the time of recovery, blood perfusion using Laser Speckle Contrast Imaging, and tissue morphology from images acquired with a Nanozoomer tissue scanner. The latter was assessed in a tissue sample taken with a biopsy punch on several days during the wound healing process. Results obtained with the Thy-1 knockout (Thy-1−/−) mice were compared with control mice. Thy-1−/− mice showed at day seven, a delayed re-epithelialization, increased micro- to macro-circulation ratio, and lower blood perfusion in the wound area. In addition, skin morphology displayed a flatter epidermis, fewer ridges, and almost no stratum granulosum or corneum, while the dermis was thicker, showing more fibroblasts and fewer lymphocytes. Our results suggest a critical role for Thy-1 in wound healing, particularly in vascular dynamics.

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Section: Methodsmentioning

confidence: 99%

The GPI-Anchored Protein Thy-1/CD90 Promotes Wound Healing upon Injury to the Skin by Enhancing Skin Perfusion

Pérez

León

López

et al. 2022

IJMS

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Section: Overall Effect Of Adenosine Receptors In Sepsismentioning

confidence: 99%

“…Numerous investigations have shown the relevance of multiple adenosine receptors in sepsis utilizing both genetic and pharmacological approaches ( 51 , 117 , 118 ). Both A2a receptor deletion mice and ZM241385 pharmacological antagonists reduced cecal ligation and puncture (CLP) induced mortality through a mechanism related to a reduced bacterial burden ( 51 , 118 ). Intriguingly, when paired with antibiotics, activation of the A2a receptor protected against sepsis created by E. coli injection, probably by inhibiting an excessive inflammatory reaction caused by the rapid drug-mediated death of vast numbers of bacteria ( 60 ).…”

Section: Overall Effect Of Adenosine Receptors In Sepsismentioning

confidence: 99%

The immunomodulatory function of adenosine in sepsis

Zhang

Yu-Jing

2022

Front. Immunol.

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Sepsis is an unsolved clinical condition with a substantial mortality rate in the hospital. Despite decades of research, no effective treatments for sepsis exists. The role of adenosine in the pathogenesis of sepsis is discussed in this paper. Adenosine is an essential endogenous molecule that activates the A1, A2a, A2b, and A3 adenosine receptors to regulate tissue function. These receptors are found on a wide range of immune cells and bind adenosine, which helps to control the immune response to inflammation. The adenosine receptors have many regulatory activities that determine the onset and progression of the disease, which have been discovered via the use of animal models. A greater understanding of the role of adenosine in modulating the immune system has sparked hope that an adenosine receptor-targeted treatment may be used one day to treat sepsis.

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“…Nevertheless, A 2A stimulation can be ambiguous in a polymicrobial infection. In a peritonitis model caused by the injection of a fecal solution, survival was higher and bacterial load was lower in A 2A -deficient animals ( Meriño et al, 2020 ). In CLP-induced sepsis, A 2A knockout or antagonism likewise enhanced survival, in addition to attenuating anti-inflammatory cytokines levels and bacterial burden in serum and peritoneal lavage fluid ( Németh et al, 2008 ).…”

Section: Recent Advances Of Purinergic Signaling In Sepsismentioning

confidence: 99%