Complement-independent Ab-induced peroxide lysis of platelets requires 12-lipoxygenase and a platelet NADPH oxidase pathway
Michael Nardi, … , Zongdong Li, Simon Karpatkin
Michael Nardi, … , Zongdong Li, Simon Karpatkin
Published April 1, 2004
Citation Information: J Clin Invest. 2004;113(7):973-980. https://doi.org/10.1172/JCI20726.
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Article AIDS/HIV

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

Abstract

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.

Authors

Michael Nardi, Steven J. Feinmark, Liang Hu, Zongdong Li, Simon Karpatkin

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Effect of anti–GPIIIa49–66 and 12(S)-HETE on platelet count and fragment...
Effect of anti–GPIIIa49–66 and 12(S)-HETE on platelet count and fragmentation of WT, NADPH oxidase gp91phox–/–, Rac-2–/–, and 12-LO–/– platelets. (A) Platelet count. Mice were treated with 25 μg of control or patient anti–GPIIIa49–66, and platelet counts were monitored at various time intervals (n = 5 for each group). (B) Fragmentation. Percentage of platelet particles were enumerated after in vitro exposure to anti–GPIIIa49–66 (25 μg/ml) (Ga), control IgG (Cg), or 12(S)-HETE (100 nM) (H) for 4 hours at 37°C.