Complement-independent Ab-induced peroxide lysis of platelets requires 12-lipoxygenase and a platelet NADPH oxidase pathway

Antiplatelet GPIIIa49-66 Ab of HIV-related thrombocytopenic patients induces thrombocytopenia and platelet fragmentation by the generation of peroxide and other reactive oxygen species (ROS). Here we report the presence of a functional platelet NADPH oxidase pathway that requires activation by the p...

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Published inThe Journal of clinical investigation Vol. 113; no. 7; pp. 973 - 980
Main Authors Nardi, Michael, Feinmark, Steven J, Hu, Liang, Li, Zongdong, Karpatkin, Simon
Format Journal Article
LanguageEnglish
Published United States American Society for Clinical Investigation 01.04.2004
Subjects
Antibodies - immunology
Arachidonate 12-Lipoxygenase - metabolism
Biomedical research
Blood Platelets - immunology
Blood Platelets - metabolism
Complement System Proteins - metabolism
Enzymes
Flow cytometry
Granulocytes
HIV Infections - metabolism
HIV-1
Humans
Kinases
NADP - metabolism
NADPH Oxidases - metabolism
Oxidation-Reduction
Patients
Proteins
Protons
Reactive Oxygen Species - metabolism
Thrombocytopenia
Thrombocytopenia - metabolism
Whooping cough
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Summary:Antiplatelet GPIIIa49-66 Ab of HIV-related thrombocytopenic patients induces thrombocytopenia and platelet fragmentation by the generation of peroxide and other reactive oxygen species (ROS). Here we report the presence of a functional platelet NADPH oxidase pathway that requires activation by the platelet 12-lipoxygenase (12-LO) pathway to fragment platelets. A new Ab-mediated mechanism is described in which the platelet 12-LO product, 12(S)-HETE activates the NADPH oxidase pathway to generate ROS.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI20726