Blunt chest trauma resulting in pulmonary contusion is a common but poorly understood injury. We previously demonstrated that lung contusion activates localized and systemic innate immune mechanisms and recruits neutrophils to the injured lung. We hypothesized that the innate immune and inflammatory activation of neutrophils may figure prominently in the response to lung injury. To investigate this, we used a model of pulmonary contusion in the mouse that is similar to that observed clinically in humans and evaluated postinjury lung function and pulmonary neutrophil recruitment. Comparisons were made between injured mice with and without neutrophil depletion. We further examined the role of chemokines and adhesion receptors in neutrophil recruitment to the injured lung. We found that lung injury and resultant physiological dysfunction after contusion were dependent on the presence of neutrophils in the alveolar space. We show that CXCL1, CXCL2/3, and CXCR2 are involved in neutrophil recruitment to the lung after injury and that intercellular adhesion molecule 1 is locally expressed and actively participates in this process. Injured gp91phox-deficient mice showed improved lung function, indicating that oxidant production by neutrophil NADPH oxidase mediates lung dysfunction after contusion. These data suggest that both neutrophil presence and function are required for lung injury after lung contusion.
*Departments of General Surgery, †Microbiology and Immunology, and ‡Internal Medicine, Section on Molecular Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina
Received 17 Dec 2010; first review completed 4 Jan 2011; accepted in final form 2 Feb 2011
Address reprint requests to J. Jason Hoth, MD, PhD, Department of General Surgery, Wake Forest University Health Sciences, Medical Center Blvd, Winston-Salem, NC 27157. E-mail: email@example.com.
This work was supported, in part, by the WFUSM Venture Fund, the American College of Surgeons C. James Carrico Faculty Research Fellowship, ALA RG-52711-N, GM083154, and Clowes ACS/AAST/NIGMS Mentored Clinical Scientist Award (J.J.H.), AI057770 (E.M.H.), RR023570 (C.E.M.), and AI065791 (C.E.M., B.K.Y.).