Platelet–Monocyte Aggregates: Understanding Mechanisms and Functions in Sepsis

ABSTRACT: Platelets have been shown to play an important immunomodulatory role in the pathogenesis of various diseases through their interactions with other immune and nonimmune cells. Sepsis is a major cause of death in the United States, and many of the mechanisms driving sepsis pathology are still unresolved. Monocytes have recently received increasing attention in sepsis pathogenesis, and multiple studies have associated increased levels of platelet-monocyte aggregates observed early in sepsis with clinical outcomes in sepsis patients. These findings suggest platelet-monocyte aggregates may be an important prognostic indicator. However, the mechanisms leading to platelet interaction and aggregation with monocytes, and the effects of aggregation during sepsis are still poorly defined. There are few studies that have really investigated functions of platelets and monocytes together, despite a large body of research showing separate functions of platelets and monocytes in inflammation and immune responses during sepsis. The goal of this review is to provide insights into what we do know about mechanisms and biological meanings of platelet-monocyte interactions, as well as some of the technical challenges and limitations involved in studying this important potential mechanism in sepsis pathogenesis. Improving our understanding of platelet and monocyte biology in sepsis may result in identification of novel targets that can be used to positively affect outcomes in sepsis.