title: Mechanism of neutrophil recruitment to the lung after pulmonary contusion.
abstract: 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 gp91-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.
authors.affiliation: Department of General Surgery, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157, USA. jhoth@wfubmc.edu
authors.forename: J Jason
authors.initials: JJ
authors.lastname: Hoth
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Wells
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Hiltbold
authors.forename: Charles E
authors.initials: CE
authors.lastname: McCall
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Yoza
mesh_terms: D000818:Animals; D054360:Chemokine CXCL1 / Q000502:physiology; D054426:Chemokine CXCL2 / Q000502:physiology; D019743:Chemokines, CXC / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D008168:Lung / Q000276:immunology* / Q000503:physiopathology; D055370:Lung Injury / Q000276:immunology* / Q000503:physiopathology*; D008562:Membrane Glycoproteins / Q000172:deficiency; D051379:Mice; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency; D020556:Neutrophil Infiltration / Q000276:immunology*; D023063:Receptors, Interleukin-8B / Q000502:physiology; D014949:Wounds, Nonpenetrating / Q000276:immunology
chemical_list: D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D008562:Membrane Glycoproteins; D023063:Receptors, Interleukin-8B; D018799:Intercellular Adhesion Molecule-1; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases