Platelet P2Y(12) signalling pathway in the dysregulated immune response during sepsis

Sepsis is a complicated pathological condition in response to severe infection. It is characterized by a strong systemic inflammatory response, where multiple components of the immune system are involved. Currently, there is no treatment for sepsis. Blood platelets are known for their role in haemostasis, but they also 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 P2Y(12) antagonists has been evaluated as a possible treatment for sepis. It was found that blocking P2Y(12) receptors decreased platelet marker expression and limited attachment to immune cells in some studies, but not in others. This review addresses the role of platelets in sepsis and discusses whether antagonizing P2Y(12) signalling pathways can alter the disease outcome. Challenges in studying P2Y(12) antagonists in sepsis also are discussed.

Automated summary

Sepsis is a complex pathological response to severe infection, characterized by a strong systemic inflammatory response involving multiple components of the immune system. Blood platelets, known for their role in haemostasis, have also been found to be involved in inflammation in septic patients. Antiplatelet therapy with P2Y(12) antagonists has been explored as a potential treatment for sepsis, but studies have yielded conflicting results regarding its effectiveness. This review discusses the role of platelets in sepsis and the potential of targeting P2Y(12) signalling pathways as a therapeutic approach.