Purinergic P2X7 receptor expression increases in leukocytes from intra-abdominal septic patients

Helios Martinez-Banaclocha,Carlos Garcia-Palenciano,Laura Martinez-Alarcon,Joaquin Amores-Iniesta,Fatima Martin-Sanchez, Giovanni A. Ercole, Ada Gonzalez-Lisorge, Jose Fernandez-Pacheco, Piedad Martinez-Gil, Julio Padilla-Rodriguez,Alberto Baroja-Mazo,Pablo Pelegrin,Juan Jose Martinez-Garcia

FRONTIERS IN IMMUNOLOGY(2023)

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摘要
Inflammation is a tightly coordinated response of the host immune system to bacterial and viral infections, triggered by the production of inflammatory cytokines. Sepsis is defined as a systemic inflammatory response followed by immunosuppression of the host and organ dysfunction. This imbalance of the immune response increases the risk of mortality of patients with sepsis, making it a major problem for critical care units worldwide. The P2X7 receptor plays a crucial role in activating the immune system by inducing the activation of peripheral blood mononuclear cells. In this study, we analyzed a cohort of abdominal origin septic patients and found that the expression of the P2X7 receptor in the plasma membrane is elevated in the different subsets of lymphocytes. We observed a direct relationship between the percentage of P2X7-expressing lymphocytes and the early inflammatory response in sepsis. Additionally, in patients whose lymphocytes presented a higher percentage of P2X7 surface expression, the total lymphocytes populations proportionally decreased. Furthermore, we found a correlation between elevated soluble P2X7 receptors in plasma and inflammasome-dependent cytokine IL-18. In summary, our work demonstrates that P2X7 expression is highly induced in lymphocytes during sepsis, and this correlates with IL-18, along with other inflammatory mediators such as IL-6, IL-8, and procalcitonin.
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关键词
sepsis,inflammation,purinergic signaling,danger signals,leukocytes
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