The effect of C1-inhibitor in a murine model of transfusion-related acute lung injury

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 C1‐inhibitor attenuates lung injury in a ‘two‐hit’ TRALI model. Methods Mice were primed with lipopolysaccharid...

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Bibliographic Details
Published in:Vox sanguinis 2014-07, Vol.107 (1), p.71-75
Main Authors: Müller, M. C. A., Stroo, I., Wouters, D., Zeerleder, S. S., Roelofs, J. J. T. H., Boon, L., Vroom, M. B., Juffermans, N. P.
Format: Article
Language:English
Subjects:
Acute Lung Injury - drug therapy
Acute Lung Injury - etiology
Acute Lung Injury - pathology
Analysis of Variance
Animals
Antibodies - immunology
Blood transfusions
Bronchoalveolar Lavage Fluid - immunology
C1-inhibitor
complement
Complement Activation - immunology
Complement C1 Inhibitor Protein - administration & dosage
Complement C3a - immunology
Complement C5a - immunology
Cytokines
Cytokines - immunology
Disease Models, Animal
Lipopolysaccharides
Lung - metabolism
Lung - pathology
Lungs
Male
MHC-I antibody
Mice
Mice, Inbred BALB C
Morbidity
Mortality
Rodents
transfusion
Transfusion Reaction - drug therapy
Transfusion Reaction - pathology
transfusion-related acute lung injury
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Summary: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 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. Conclusion 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.
ISSN:0042-9007
1423-0410
DOI:10.1111/vox.12128