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Activation of platelet protein kinase C by ultraviolet light B mediates platelet transfusion-related acute lung injury in a two-event animal model.
MedLine Citation:
PMID:  22853798     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: We recently reported that infusion of ultraviolet light B (UVB)-exposed human platelets (HPs) can be the second event that mediates acute lung injury (ALI) in a two-event mouse model of transfusion-related acute lung injury (mTRALI). We have now identified changes in HPs induced by UVB light and responses of the recipient animal that mediate the mTRALI. STUDY DESIGN AND METHODS: Effects of UVB on HPs were monitored by flow cytometry and aggregation. HPs exposed to UVB, with or without inhibitors to specific biochemical pathways, were infused into lipopolysaccharide (LPS)-primed severe combined immunodeficient (SCID) mice. ALI was monitored by protein elevations in bronchoalveolar lavage fluid (BALF). RESULTS: UVB increased fibrinogen binding and potentiated HP aggregation. Infusion of UVB HPs into LPS-primed SCID mice led to macrophage inflammatory protein 2 (MIP-2) elevations in plasma and BALF and resulted in ALI. Protein kinase C (PKC) inhibitors prevented UVB-induced HP changes in vitro and reduced MIP-2 elevation and mTRALI in vivo. Blocking of fibrinogen binding to HP αIIbβ3 with c7E3 monoclonal antibody prevented mTRALI. MIP-2 elevation in vivo in response to UVB HPs was essential for ALI since blocking of MIP-2 receptor in vivo prevented mTRALI. CONCLUSION: PKC signaling mediates UVB-induced HP fibrinogen binding and aggregation in vitro. The host animal responds to an infusion of UVB HPs by MIP-2 elevation that mediates downstream mTRALI. Elucidation of molecular mechanisms in UVB HP-mediated mTRALI may provide insight into pulmonary adverse events reported with UV-irradiated pathogen-reduced platelets.
Authors:
Li Zhi; Xuan Chi; Monique P Gelderman; Jaroslav G Vostal
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-31
Journal Detail:
Title:  Transfusion     Volume:  -     ISSN:  1537-2995     ISO Abbreviation:  Transfusion     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-8-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0417360     Medline TA:  Transfusion     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 American Association of Blood Banks.
Affiliation:
From the Laboratory of Cellular Hematology, Division of Hematology, OBRR, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland.
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