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

Leytin, Valery ; Mykhaylov, Sergiy ; Starkey, Alison F ; Allen, David J ; Lau, Herbert ; Ni, Heyu ; Semple, John W LU ; Lazarus, Alan H and Freedman, John (2006) In British Journal of Haematology 133(1). p.78-82
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... (More)

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.

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author
; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
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
in
British Journal of Haematology
volume
133
issue
1
pages
78 - 82
publisher
Wiley-Blackwell
external identifiers
  • pmid:16512832
  • scopus:33644639028
ISSN
0007-1048
DOI
10.1111/j.1365-2141.2006.05981.x
language
English
LU publication?
no
id
36f9b66a-e636-4dcf-b019-e99a0d15674f
date added to LUP
2022-11-09 15:24:46
date last changed
2024-01-03 18:43:36
@article{36f9b66a-e636-4dcf-b019-e99a0d15674f,
  abstract     = {{<p>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.</p>}},
  author       = {{Leytin, Valery and Mykhaylov, Sergiy and Starkey, Alison F and Allen, David J and Lau, Herbert and Ni, Heyu and Semple, John W and Lazarus, Alan H and Freedman, John}},
  issn         = {{0007-1048}},
  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}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{78--82}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{British Journal of Haematology}},
  title        = {{Intravenous immunoglobulin inhibits anti-glycoprotein IIb-induced platelet apoptosis in a murine model of immune thrombocytopenia}},
  url          = {{http://dx.doi.org/10.1111/j.1365-2141.2006.05981.x}},
  doi          = {{10.1111/j.1365-2141.2006.05981.x}},
  volume       = {{133}},
  year         = {{2006}},
}