title: Protein-based therapies for acute lung injury: targeting neutrophil extracellular traps.
abstract: BACKGROUND
  Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the acute onset of noncardiac respiratory insufficiency associated with bilateral lung infiltrations. During the past decade, mechanical ventilation strategies using low tidal volumes have reduced the mortality of ALI/ARDS to ∼ 20 - 40%. However, ALI/ARDS continues to be a major factor in global burden of diseases, with no pharmacological agents currently available.
  
  
  METHODS
  In this review, we discuss several inflammatory proteins involved in the molecular pathogenesis of ALI/ARDS. The complement cleavage product, C5a, is a peptide acting as a potent anaphylatoxin. C5a may trigger the formation of neutrophil extracellular traps (NETs) and release of histone proteins to the extracellular compartment during ALI/ARDS. NETs may activate platelets to release TGF-β, which is involved in tissue remodeling during the later phases of ALI/ARDS. Interception of C5a signaling or blockade of extracellular histones has recently shown promising beneficial effects in small animal models of ALI/ARDS.
  
  
  CONCLUSIONS
  Novel protein-based strategies for the treatment of ALI/ARDS may inspire the hopes of scientists, clinicians, and patients. Although neutralization of extracellular histones/NETs, C5a, and TGF-β is effective in experimental models of ALI/ARDS, controlled clinical trials will be necessary for further evaluation in future.
authors.affiliation: University Medical Center, Center for Thrombosis and Hemostasis , Langenbeckstrasse 1, Mainz, 55131 , Germany +49 6131 17 8277 ; +49 6131 17 6238 ; markus.bosmann@unimedizin-mainz.demailto.
authors.forename: Markus
authors.initials: M
authors.lastname: Bosmann
authors.forename: Peter A
authors.initials: PA
authors.lastname: Ward
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy*; D000818:Animals; D002986:Clinical Trials as Topic; D015936:Complement C5a / Q000037:antagonists & inhibitors / Q000502:physiology; D065206:Extracellular Traps / Q000187:drug effects*; D006801:Humans; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D053773:Transforming Growth Factor beta1; D015936:Complement C5a
keywords: C5a; TGF-β; antibody; extracellular histones; inflammation; neutrophil extracellular traps