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

J Clin Invest. 2004 Apr;113(7):973-80. doi: 10.1172/JCI20726.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies / immunology*
  • Arachidonate 12-Lipoxygenase / metabolism*
  • Blood Platelets / immunology
  • Blood Platelets / metabolism*
  • Complement System Proteins / metabolism
  • HIV Infections / metabolism
  • HIV-1
  • Humans
  • NADP / metabolism
  • NADPH Oxidases / metabolism*
  • Oxidation-Reduction
  • Reactive Oxygen Species / metabolism
  • Thrombocytopenia / metabolism

Substances

  • Antibodies
  • Reactive Oxygen Species
  • NADP
  • Complement System Proteins
  • Arachidonate 12-Lipoxygenase
  • NADPH Oxidases