| Activation of platelet protein kinase C by ultraviolet light B mediates platelet transfusion-related acute lung injury in a two-event animal model. | |
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MedLine Citation:
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PMID: 22853798 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Li Zhi; Xuan Chi; Monique P Gelderman; Jaroslav G Vostal |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-7-31 |
Journal Detail:
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Title: Transfusion Volume: - ISSN: 1537-2995 ISO Abbreviation: Transfusion Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-8-2 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0417360 Medline TA: Transfusion Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 American Association of Blood Banks. |
Affiliation:
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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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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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