title: Role of Complement C5 in Experimental Blunt Chest Trauma-Induced Septic Acute Lung Injury (ALI).
abstract: BACKGROUND
  Severe blunt chest trauma is associated with high mortality. Sepsis represents a serious risk factor for mortality in acute respiratory distress syndrome (ARDS). In septic patients with ARDS complement activation products were found to be elevated in the plasma. In single models like LPS or trauma complement has been studied to some degree, however in clinically highly relevant double hit models such as the one used here little data is available. Here, we hypothesized that absence of C5 is correlated with a decreased inflammatory response in trauma induced septic acute lung injury.
  
  
  METHODS
  12 hrs after DH in mice the local and systemic cytokines and chemokines were quantified by multiplex bead array or ELISA, activated caspase-3 by western blot. Data were analyzed using one-way ANOVA followed by post-hoc Sidak's multiple comparison test (significance, p≤ 0.05).
  
  
  RESULTS
  In lung tissue interleukin (IL)-6, monocyte chemo attractant protein-1 (MCP-1) and granulocyte-colony stimulating factor (G-CSF) was elevated in both C5-/- mice and wildtype littermates (wt), whereas caspase-3 was reduced in lungs after DH in C5-/- mice. Systemically, reduced keratinocyte-derived chemokine (KC) levels were observed after DH in C5-/- compared to wt mice. Locally, lung myeloperoxidase (MPO), protein, IL-6, MCP-1 and G-CSF in brochoalveolar lavage fluid (BALF) were elevated after DH in C5-/- compared to wt.
  
  
  CONCLUSIONS
  In the complex but clinically relevant DH model the local and systemic inflammatory immune response features both, C5-dependent and C5-independent characteristics. Activation of caspase-3 in lung tissue after DH was C5-dependent whereas local inflammation in lung tissue was C5-independent.
authors.affiliation: Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery, Center of Surgery, University of Ulm, Ulm, Germany.
authors.forename: Miriam
authors.identifier: http://orcid.org/0000-0002-1474-0785
authors.initials: M
authors.lastname: Kalbitz
authors.affiliation: Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery, Center of Surgery, University of Ulm, Ulm, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Karbach
authors.affiliation: Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery, Center of Surgery, University of Ulm, Ulm, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Braumueller
authors.affiliation: Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery, Center of Surgery, University of Ulm, Ulm, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Kellermann
authors.affiliation: Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery, Center of Surgery, University of Ulm, Ulm, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Gebhard
authors.affiliation: Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery, Center of Surgery, University of Ulm, Ulm, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Huber-Lang
authors.affiliation: Department of Traumatology, Hand-, Plastic-, and Reconstructive Surgery, Center of Surgery, University of Ulm, Ulm, Germany.|Orthopedic Trauma, BG-Trauma Center Murnau, Murnau, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Perl
mesh_terms: D055371:Acute Lung Injury / Q000235:genetics* / Q000473:pathology; D000818:Animals; D053148:Caspase 3 / Q000096:biosynthesis; D018932:Chemokine CCL2 / Q000096:biosynthesis; D003182:Complement C5 / Q000235:genetics* / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics* / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D012128:Respiratory Distress Syndrome / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D018805:Sepsis / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000473:pathology; D013898:Thoracic Injuries / Q000235:genetics / Q000473:pathology; D014949:Wounds, Nonpenetrating / Q000235:genetics
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D003182:Complement C5; D015850:Interleukin-6; D016179:Granulocyte Colony-Stimulating Factor; D053148:Caspase 3