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The effect of C1‐inhibitor in a murine model of transfusion‐related acute lung injury
Author(s) -
Müller M. C. A.,
Stroo I.,
Wouters D.,
Zeerleder S. S.,
Roelofs J. J. T. H.,
Boon L.,
Vroom M. B.,
Juffermans N. P.
Publication year - 2014
Publication title -
vox sanguinis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.68
H-Index - 83
eISSN - 1423-0410
pISSN - 0042-9007
DOI - 10.1111/vox.12128
Subject(s) - transfusion related acute lung injury , bronchoalveolar lavage , medicine , lung , immunology , antibody , lipopolysaccharide , complement system , mechanical ventilation , pharmacology , anesthesia , pulmonary edema
Background and objective Transfusion‐related acute lung injury ( TRALI ) is the leading cause of transfusion‐related morbidity and mortality. Specific therapy is lacking. We assessed whether C 1‐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, C 1‐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 C 3a and C 5a. Administration of C 1‐inhibitor resulted in increased pulmonary C 1‐inhibitor levels with high activity. C 1‐inhibitor reduced pulmonary levels of complement C 3a associated with improved lung injury scores. However, levels of pro‐inflammatory mediators were unaffected. Conclusion In a murine model of TRALI , C 1‐inhibitor attenuated pulmonary levels of C 3a associated with improved lung injury scores, but with persistent high levels of inflammatory cytokines.