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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Figure 1

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Absence of granulocytes and presence of the NADPH oxidase component gp91...
Absence of granulocytes and presence of the NADPH oxidase component gp91phox in gel-filtered platelets. (A) Fluorescence flow-cytometry comparison of a leukocyte/platelet preparation with gel-filtered platelets. Lower-left panel: forward scatter–side scatter plot of an enriched leukocyte/platelet preparation. G, granulocytes; L, lymphocytes; Pl, platelets, as designated by their known scatter pattern. Upper-left panel: similar plot of gel-filtered platelets. Lower-right panel: anti–CD11b-FITC Ab reactivity specific for granulocytes/monocytes. Upper-right panel: similar plot of gel-filtered platelets. Granulocyte-reactive anti–CD11b-FITC Ab was unreactive with gel-filtered platelets (<0.1%). FSH, forward scatter height; SSH, side scatter height. (B) Reactivity of anti–gp91 Ab with granulocytes and platelets. Upper panels: control mouse mAb, reactivity with platelets and granulocytes. Lower panels: monoclonal anti–gp91 fluorescence.