Platelet P2Y₁₂ signalling pathway in the dysregulated immune response during sepsis

Abstract

Sepsis is a complicated pathological condition in response to severe infections. It is characterized by a strong systemic inflammatory response and multiple components of the immune system are involved. Currently, there is no treatment for sepsis. Platelets are known for their role in hemostasis but they participate in inflammation through cell‐cell interaction and the secretion of inflammatory mediators. Interestingly, an increase in platelet activation, secretion, and aggregation with other immune cells such as monocytes, T lymphocytes, and neutrophils, has been detected in septic patients. Therefore, antiplatelet therapy in terms of P2Y12 antagonists has been evaluated as a possible treatment for sepsis. Overall, blocking P2Y12 decreased platelet marker expression limiting attachment to immune cells in certain studies, but not others. This review underlines the role of platelets during sepsis and whether antagonizing the P2Y12 signaling pathways can alter the outcome. Challenges in studying P2Y12 antagonists in sepsis will also be discussed.

Platelet purinergic receptors and non‐thrombotic diseases

“…The understanding of platelet activation via P2Y 12 receptors, in the context of inflammation is discussed in cardiovascular and non-cardiovascular conditions, recognizing that direct and pleotropic effects of thienopyridines and ticagrelor can make the pharmacological interpretation of clinical studies complex (Parker & Storey, 2024). This is complemented by a review of evidence for activation of P2Y 12 receptors in the dysregulated immune response during sepsis and the challenges associated with interpreting a dynamically changing inflammatory and then conversely immunosuppressed state, combined with activation of haemostatic pathways by Amoafo and colleagues (Amoafo et al, 2024). In another review, the potential role of adenosine is discussed (Boncler et al, 2024).…”