The Molecular and Cellular Response to Pulmonary Contusion

Multi-system trauma is a significant source of patient morbidity and mortality, accounting for 140,000 deaths annually. Thoracic injuries occur in the majority of blunt trauma patients and are present in up to 75% of all trauma-related deaths. Pulmonary contusion is a common and potentially lethal manifestation of blunt chest trauma, affecting 10-17% of all trauma admissions with estimates of mortality between 10-25%. The mechanisms responsible for both the local and systemic inflammatory processes associated with pulmonary contusion are poorly understood. There is mounting evidence that the lung injury is also inflammatory in nature. In addition to structural damage to the lung, an inflammatory cell infiltrate composed primarily of neutrophils ensues. Various inflammatory mediators are then produced, and dysfunction occurs in immunocompetent cell populations located both within the lung and remotely. Alterations in apoptosis, defective bacterial clearance, and an increased susceptibility to subsequent septic challenge have been described after lung contusion. Despite advances in our understanding of the pathogenesis of pulmonary contusion, there has been little meaningful improvement in outcome. Specifically lacking is an understanding of the mechanisms responsible for the inflammatory response to pulmonary contusion. This is due to several factors, including an inadequate characterization of the pathobiology at the molecular and cellular level, and a deficiency of valid small animal models in which to study this injury. In this study, we establish reproducible rodent models for blunt chest trauma that results in a physiological significant injury with lung dysfunction. We develop a paradigm of innate immune responses to blunt chest trauma that involve activation of inflammatory mediators, like CXC chemokines, that participate in the recruitment of neutrophils to the lung after injury. We found that neutrophil accumulation occurs and correlates with the severity of lung dysfunction. The innate immune response to pulmonary contusion was found, at least in part, to activate TLR dependent responses that we characterize herein.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2009

Author dc:creator

• Hoth, James

• Trauma, Pulmonary Contusion, Toll-like Receptor, Innate Immunity, Second Hit, Priming, Neutrophil

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/10339/14677

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/14677