Complement system

Abstract

Severe trauma, followed by substantial blood loss or sepsis, represents a major cause of mortality and morbidity. Massive concurrent activation of the hemostatic and complement systems is a common denominator of trauma and sepsis, and the intimate crosstalk between these two immune mechanisms augments their biological effects. While local activation of these proteolytic cascades contributes to the host defense, their uncontrolled systemic activation has major tissue damaging effects leading to trauma-induced coagulopathies and complementopathies, multiple organ failure, and ultimately death. This chapter reviews the molecular pathways of complement activation, the regulatory mechanisms controlling the formation of the terminal cytolytic complex C5b-9, and the signaling events triggered by the complement-derived anaphylatoxins. The crosstalk between complement and coagulation and the contribution of these pathways to the integrated host response to injury and sepsis are discussed.