Molecular mechanisms of inflammation and tissue injury after major trauma-is complement the "bad guy"?

Journal of Biomedical Science

Review

Sebastian Weckbach¹  Michael A Flierl¹  Miriam D Neher¹  Philip F Stahel²  Markus S Huber-Lang³ 

[1] Department of Orthopaedic Surgery, University of Colorado Denver, School of Medicine, Denver Health Medical Center, 777 Bannock Street, 80204, Denver, CO, USA;Department of Orthopaedic Surgery, University of Colorado Denver, School of Medicine, Denver Health Medical Center, 777 Bannock Street, 80204, Denver, CO, USA;Department of Neurosurgery, University of Colorado Denver, School of Medicine, Denver Health Medical Center, 777 Bannock Street, 80204, Denver, CO, USA;Department of Orthopaedic Trauma, Hand, Plastic, and Reconstructive Surgery, University Hospital Ulm, Steinhövelstraße 9, D-89075, Ulm, Germany;

关键词: Traumatic Brain Injury;    Acute Lung Injury;    Complement Activation;    Major Trauma;    Closed Head Injury;   

DOI  :  10.1186/1423-0127-18-90

 received in 2011-10-08, accepted in 2011-11-30,  发布年份 2011

来源: Springer

【 摘 要 】

Trauma represents the leading cause of death among young people in industrialized countries. Recent clinical and experimental studies have brought increasing evidence for activation of the innate immune system in contributing to the pathogenesis of trauma-induced sequelae and adverse outcome. As the "first line of defense", the complement system represents a potent effector arm of innate immunity, and has been implicated in mediating the early posttraumatic inflammatory response. Despite its generic beneficial functions, including pathogen elimination and immediate response to danger signals, complement activation may exert detrimental effects after trauma, in terms of mounting an "innocent bystander" attack on host tissue. Posttraumatic ischemia/reperfusion injuries represent the classic entity of complement-mediated tissue damage, adding to the "antigenic load" by exacerbation of local and systemic inflammation and release of toxic mediators. These pathophysiological sequelae have been shown to sustain the systemic inflammatory response syndrome after major trauma, and can ultimately contribute to remote organ injury and death. Numerous experimental models have been designed in recent years with the aim of mimicking the inflammatory reaction after trauma and to allow the testing of new pharmacological approaches, including the emergent concept of site-targeted complement inhibition. The present review provides an overview on the current understanding of the cellular and molecular mechanisms of complement activation after major trauma, with an emphasis of emerging therapeutic concepts which may provide the rationale for a "bench-to-bedside" approach in the design of future pharmacological strategies.

【 授权许可】

Unknown   
© Neher et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.