Home WakeSpace Scholarship › Electronic Theses and Dissertations

The Molecular and Cellular Response to Pulmonary Contusion

Electronic Theses and Dissertations

Item Files

Item Details

abstract
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.
subject
Trauma, Pulmonary Contusion, Toll-like Receptor, Innate Immunity, Second Hit, Priming, Neutrophil
Immunology, Molecular Biology
contributor
Hoth, James (author)
Hiltbold, Elizabeth (committee chair)
McCall, Charles (committee member)
McPhail, Linda (committee member)
Yoza, Barbara (committee member)
Seeds, Michael (committee member)
date
2009-08-07T14:19:41Z (accessioned)
2010-06-18T18:57:14Z (accessioned)
2009-08-07T14:19:41Z (available)
2010-06-18T18:57:14Z (available)
2009-08-07T14:19:41Z (issued)
degree
Molecular Medicine (discipline)
identifier
http://hdl.handle.net/10339/14677 (uri)
language
en_US (iso)
publisher
Wake Forest University
rights
Release the entire work for access only to the Wake Forest University system for one year from the date below. After one year, release the entire work for access worldwide. (accessRights)
title
The Molecular and Cellular Response to Pulmonary Contusion
type
Dissertation

Usage Statistics