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.
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-inhibitorattenuates 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.
Authors: Ingrid Stroo; Jack Yang; Adam A Anas; J Daan de Boer; Gerard van Mierlo; Dorina Roem; Diana Wouters; Ruchira Engel; Joris J T H Roelofs; Cornelis van 't Veer; Tom van der Poll; Sacha Zeerleder Journal: PLoS One Date: 2017-10-16 Impact factor: 3.240
Authors: Magdielis Gregory Rivera; Alana C Sampson; Pamela S Hair; Haree K Pallera; Kaitlyn G Jackson; Adrianne I Enos; Turaj Vazifedan; Alice L Werner; Corinne L Goldberg; Frank A Lattanzio; Kenji M Cunnion; Neel K Krishna Journal: PLoS One Date: 2020-04-20 Impact factor: 3.240
Authors: Ilse Jongerius; Leendert Porcelijn; Anna E van Beek; John W Semple; C Ellen van der Schoot; Alexander P J Vlaar; Rick Kapur Journal: Transfus Med Rev Date: 2019-10-18