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 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.
Nardi
Michael
M
Department of Pediatrics, New York University School of Medicine, New York, New York 10016, USA.
Feinmark
Steven J
SJ
Hu
Liang
L
Li
Zongdong
Z
Karpatkin
Simon
S
D000906:Antibodies / Q000276:immunology*; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism*; D003165:Complement System Proteins / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D009249:NADP / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D013921:Thrombocytopenia / Q000378:metabolism
D000906:Antibodies; D017382:Reactive Oxygen Species; D009249:NADP; D003165:Complement System Proteins; D001092:Arachidonate 12-Lipoxygenase; D019255:NADPH Oxidases