Danger signals activating the immune response after trauma.
Sterile injury can cause a systemic inflammatory response syndrome (SIRS) that resembles the host response during sepsis. The inflammatory response following trauma comprises various systems of the human body which are cross-linked with each other within a highly complex network of inflammation. Endogenous danger signals (danger-associated molecular patterns; DAMPs; alarmins) as well as exogenous pathogen-associated molecular patterns (PAMPs) play a crucial role in the initiation of the immune response. With popularization of the "danger theory," numerous DAMPs and PAMPs and their corresponding pathogen-recognition receptors have been identified. In this paper, we highlight the role of the DAMPs high-mobility group box protein 1 (HMGB1), interleukin-1α (IL-1α), and interleukin-33 (IL-33) as unique dual-function mediators as well as mitochondrial danger signals released upon cellular trauma and necrosis.
Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, 8091 Zurich, Switzerland.
Stefanie
S
Hirsiger
Hans-Peter
HP
Simmen
Clément M L
CM
Werner
Guido A
GA
Wanner
Daniel
D
Rittirsch
D000818:Animals; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D053582:Interleukin-1alpha / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism; D015398:Signal Transduction; D014947:Wounds and Injuries / Q000378:metabolism* / Q000503:physiopathology*
D024243:HMGB1 Protein; C506536:IL33 protein, human; D053582:Interleukin-1alpha; D000067596:Interleukin-33; D007378:Interleukins