Abstract
Background
Megakaryocytes are traditionally recognized as cells responsible for platelet production. However, beyond their role in thrombopoiesis, megakaryocytes also participate in inflammatory responses and regulate immune system functions. Sepsis, characterized by life-threatening organ dysfunction due to a dysregulated response to infection, prominently features coagulopathy, severe inflammation, and immune dysfunction as key pathophysiological aspects.
Aim of review
Given the diverse functions of megakaryocytes, we explore their roles in coagulation in the context of sepsis, and also in inflammatory and immune regulation. We try to infer future research directions and potential strategies for sepsis prevention and treatment based on the properties of megakaryocytes.
Key scientific concepts of review
The purpose of this review is to both highlight and provide an update on the functions of megakaryocytes and pathophysiological changes in sepsis. Specific emphasis is given to the role of megakaryocytes in sepsis, which suggests value of future research and clinical application.
Key Points
- Megakaryocyte Functions: Beyond platelet production, megakaryocytes participate in immune modulation by expressing genes involved in pathogen recognition and cytokine production.
- Role in Coagulation: Megakaryocytes contribute to thrombopoiesis and thrombotic disorders via platelet production and interactions with neutrophils and endothelial cells, influencing immunothrombosis.
- Inflammatory Mediators: They secrete inflammatory cytokines, including TNF-α and IL-1β, and amplify systemic inflammation during sepsis.
- Immune Interactions: Acting as antigen-presenting cells (APCs), megakaryocytes influence both innate and adaptive immunity by interacting with T and B cells and promoting neutrophil extracellular trap (NET) formation.
- Thrombopoiesis in Sepsis: Sepsis-induced alterations in thrombopoiesis include enhanced platelet production during acute inflammation and diminished activity due to mitochondrial dysfunction in severe cases.
- Location-Specific Roles: Lung megakaryocytes demonstrate unique immune and antigen-presenting functions, while bone marrow and spleen megakaryocytes primarily support thrombopoiesis.
- Diagnostic Implications: Megakaryocyte-derived extracellular vesicles (EVs) and cytokines could serve as biomarkers for early detection and prognosis of sepsis.
- Therapeutic Targets: Potential strategies include targeting megakaryocyte-mediated pathways, such as pyroptosis and the cGAS-STING signaling axis, to modulate coagulation and immune responses.
- Gene Therapy Prospects: Advances in megakaryocyte gene engineering offer opportunities for developing targeted treatments for sepsis and related disorders.
- Research Gaps: Further studies are required to elucidate the mechanistic underpinnings of megakaryocyte activity and their therapeutic potential in sepsis management.
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