title: Innate immune response to pulmonary contusion:  identification of cell type-specific inflammatory responses.
abstract: Lung injury from pulmonary contusion is a common traumatic injury, predominantly seen after blunt chest trauma, such as in vehicular accidents. The local and systemic inflammatory response to injury includes activation of innate immune receptors, elaboration of a variety of inflammatory mediators, and recruitment of inflammatory cells to the injured lung. Using a mouse model of pulmonary contusion, we had previously shown that innate immune Toll-like receptors 2 and 4 (TLR2 and TLR4) mediate the inflammatory response to lung injury. In this study, we used chimeric mice generated by adoptive bone marrow transfer between TLR2 or TLR4 and wild-type mice. We found that, in the lung, both bone marrow-derived and nonmyeloid cells contribute to TLR-dependent inflammatory responses after injury in a cell type-specific manner. We also show a novel TLR2-dependent injury mechanism that is associated with enhanced airway epithelial cell apoptosis and increased pulmonary FasL and Fas expression in the lungs from injured mice. Thus, in addition to cardiopulmonary physiological dysfunction, cell type-specific TLR and their differential response to injury may provide novel specific targets for management of patients with pulmonary contusion.
authors.affiliation: Department of General Surgery, Section on Molecular Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA. jhoth@wakehealth.edu
authors.forename: J Jason
authors.initials: JJ
authors.lastname: Hoth
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Wells
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Yoza
authors.forename: Charles E
authors.initials: CE
authors.lastname: McCall
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D054360:Chemokine CXCL1 / Q000378:metabolism; D003288:Contusions / Q000276:immunology*; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000276:immunology*; D015850:Interleukin-6 / Q000378:metabolism; D055370:Lung Injury / Q000276:immunology* / Q000628:therapy; D051379:Mice; D018345:Mice, Knockout; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D054360:Chemokine CXCL1; D015850:Interleukin-6; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4