title: Physiological and immune-biological characterization of a long-term murine model of blunt chest trauma.
abstract: Blunt chest trauma causes pulmonary and systemic inflammation. It is still a matter of debate whether the long-term course of this inflammatory response is associated with persistent impairment of lung function. We hypothesized that an increase of inflammatory biomarkers may still be present at later time points after blunt chest trauma, eventually, despite normalized lung mechanics and gas exchange. Anesthetized spontaneously breathing male C57BL/6J mice underwent a blast wave-induced blunt chest trauma or sham procedure. Twelve and 24 h later, blood gases and lung mechanics were measured, together with blood, bronchoalveolar lavage (BAL), and tissue cytokine concentrations (multiplex cytokine kit); heme oxygenase 1 (HO-1), activated caspase-3, Bcl-xL, and Bax expression (Western blotting); nuclear factor-κB activation (electrophoretic mobility shift assay); nitrotyrosine formation; and purinergic (P2XR4 and P2XR7) receptor expression (immunohistochemistry). Histological damage was assessed by hematoxylin and eosin and periodic acid-Schiff staining. High-resolution respirometry allowed assessing mitochondrial respiration in diaphragm biopsies. Chest trauma significantly increased tissue and BAL cytokine levels, associated with a significant increase in HO-1, purinergic receptor expression, and tissue nitrotyrosine formation. In contrast, lung mechanics, gas exchange, and histological damage did not show any significant difference between sham and trauma groups. Activation of the immune response remains present at later time points after murine blunt chest trauma. Discordance of the increased local inflammatory response and preserved pulmonary function may be explained by a dissociation of the immune response and lung function, such as previously suggested after experimental sepsis.
authors.affiliation: *Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, and †Klinik für Anästhesiologie, Universitätsklinikum Ulm, Ulm, Germany; ‡Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts; §Institut für Pathologie, and ∥Klinik für Unfallchirurgie, Hand-, Plastische- und Wiederherstellungschirurgie, Universitätsklinikum Ulm; and ¶Institut für Allgemeine Physiologie, Universität Ulm, Ulm; and **Department of Pulmonary Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach a.d. Riss, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hafner
authors.forename: Katja
authors.initials: K
authors.lastname: Wagner
authors.forename: Martin
authors.initials: M
authors.lastname: Wepler
authors.forename: José
authors.initials: J
authors.lastname: Matallo
authors.forename: Michael
authors.initials: M
authors.lastname: Gröger
authors.forename: Oscar
authors.initials: O
authors.lastname: McCook
authors.forename: Angelika
authors.initials: A
authors.lastname: Scheuerle
authors.forename: Markus
authors.initials: M
authors.lastname: Huber-Lang
authors.forename: Manfred
authors.initials: M
authors.lastname: Frick
authors.forename: Sandra
authors.initials: S
authors.lastname: Weber
authors.forename: Bettina
authors.initials: B
authors.lastname: Stahl
authors.forename: Birgit
authors.initials: B
authors.lastname: Jung
authors.forename: Enrico
authors.initials: E
authors.lastname: Calzia
authors.forename: Michael
authors.initials: M
authors.lastname: Georgieff
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.forename: Paul
authors.initials: P
authors.lastname: Dietl
authors.forename: Peter
authors.initials: P
authors.lastname: Radermacher
authors.forename: Florian
authors.initials: F
authors.lastname: Wagner
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019069:Cell Respiration / Q000502:physiology; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000502:physiology; D011659:Pulmonary Gas Exchange / Q000502:physiology; D011983:Receptors, Purinergic / Q000096:biosynthesis; D015656:Respiratory Mechanics / Q000502:physiology; D013898:Thoracic Injuries / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D014949:Wounds, Nonpenetrating / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*
chemical_list: D018925:Chemokines; D016207:Cytokines; D011983:Receptors, Purinergic; C002744:3-nitrotyrosine; D014443:Tyrosine