title: The effect of C1-inhibitor in a murine model of transfusion-related acute lung injury.
abstract: OBJECTIVE
  Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality. Specific therapy is lacking. We assessed whether C1-inhibitor attenuates lung injury in a 'two-hit' TRALI model.
  
  
  METHODS
  Mice were primed with lipopolysaccharide, subsequently TRALI was induced by MHC-I antibodies. In the intervention group, C1-inhibitor was infused concomitantly. Mice were supported with mechanical ventilation. After 2 h, mice were killed, lungs were removed and bronchoalveolar lavage fluid (BALF) was obtained.
  
  
  RESULTS
  Injection of MHC-I antibodies induced TRALI, illustrated by an increase in wet-to-dry ratio of the lungs, in BALF protein levels and in lung injury scores. TRALI was further characterized by complement activation, demonstrated by increased BALF levels of C3a and C5a. Administration of C1-inhibitor resulted in increased pulmonary C1-inhibitor levels with high activity. C1-inhibitor reduced pulmonary levels of complement C3a associated with improved lung injury scores. However, levels of pro-inflammatory mediators were unaffected.
  
  
  CONCLUSIONS
  In a murine model of TRALI, C1-inhibitor attenuated pulmonary levels of C3a associated with improved lung injury scores, but with persistent high levels of inflammatory cytokines.
authors.affiliation: Department of Intensive Care Medicine and Laboratory of Experimental Intensive Care and Anesthesiology (LEICA), Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: M C A
authors.initials: MC
authors.lastname: Müller
authors.forename: I
authors.initials: I
authors.lastname: Stroo
authors.forename: D
authors.initials: D
authors.lastname: Wouters
authors.forename: S S
authors.initials: SS
authors.lastname: Zeerleder
authors.forename: J J T H
authors.initials: JJ
authors.lastname: Roelofs
authors.forename: L
authors.initials: L
authors.lastname: Boon
authors.forename: M B
authors.initials: MB
authors.lastname: Vroom
authors.forename: N P
authors.initials: NP
authors.lastname: Juffermans
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D003167:Complement Activation / Q000276:immunology; D050718:Complement C1 Inhibitor Protein / Q000008:administration & dosage*; D015926:Complement C3a / Q000276:immunology; D015936:Complement C5a / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D065227:Transfusion Reaction / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000906:Antibodies; D050718:Complement C1 Inhibitor Protein; D016207:Cytokines; D008070:Lipopolysaccharides; D015926:Complement C3a; D015936:Complement C5a
keywords: C1-inhibitor; MHC-I antibody; complement; transfusion; transfusion-related acute lung injury