Intravenous immunoglobulin inhibits anti-glycoprotein IIb-induced platelet apoptosis in a murine model of immune thrombocytopenia

Valery Leytin, Sergiy Mykhaylov, Alison F Starkey, David J Allen, Herbert Lau, Heyu Ni, John W Semple, Alan H Lazarus, John Freedman

Research output: Contribution to journalArticlepeer-review

Abstract

We have previously shown that injection of anti-glycoprotein (GP) IIb induces murine immune thrombocytopenia (ITP) and that intravenous immunoglobulin (IVIg) ameliorates ITP. We hypothesise that murine ITP may be associated with platelet apoptosis, which is upregulated by anti-GPIIb and downregulated by IVIg. The current study demonstrated that anti-GPIIb injection induced three critical apoptosis manifestations in platelets: (i) mitochondrial inner transmembrane potential (delta psi m) depolarisation; (ii) caspase-3 activation; and (iii) phosphatidylserine (PS) exposure. IVIg administration inhibited caspase-3 activation and PS exposure, but not delta psi m-depolarisation, in anti-GPIIb-treated platelets, demonstrating that IVIg ameliorates thrombocytopenia concomitantly with inhibiting late, but not early mechanisms of platelet apoptosis.

Original languageEnglish
Pages (from-to)78-82
JournalBritish Journal of Haematology
Volume133
Issue number1
DOIs
Publication statusPublished - 2006 Apr
Externally publishedYes

Free keywords

  • Animals
  • Apoptosis/drug effects
  • Autoantibodies/immunology
  • Blood Platelets/drug effects
  • Caspase 3
  • Caspases/metabolism
  • Depression, Chemical
  • Enzyme Activation
  • Immunoglobulins, Intravenous/administration & dosage
  • Immunologic Factors/administration & dosage
  • Membrane Potentials/drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mitochondrial Membranes/drug effects
  • Models, Animal
  • Phosphatidylserines/metabolism
  • Platelet Glycoprotein GPIIb-IIIa Complex/immunology
  • Thrombocytopenia/blood

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