title: Intravenous immunoglobulin inhibits anti-glycoprotein IIb-induced platelet apoptosis in a murine model of immune thrombocytopenia.
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.
authors.affiliation: Division of Transfusion Medicine, Department of Laboratory Medicine, St Michael's Hospital, Toronto, ON, Canada. leytinv@smh.toronto.on.ca
authors.forename: Valery
authors.initials: V
authors.lastname: Leytin
authors.forename: Sergiy
authors.initials: S
authors.lastname: Mykhaylov
authors.forename: Alison F
authors.initials: AF
authors.lastname: Starkey
authors.forename: David J
authors.initials: DJ
authors.lastname: Allen
authors.forename: Herbert
authors.initials: H
authors.lastname: Lau
authors.forename: Heyu
authors.initials: H
authors.lastname: Ni
authors.forename: John W
authors.initials: JW
authors.lastname: Semple
authors.forename: Alan H
authors.initials: AH
authors.lastname: Lazarus
authors.forename: John
authors.initials: J
authors.lastname: Freedman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001323:Autoantibodies / Q000276:immunology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003864:Depression, Chemical; D004789:Enzyme Activation; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D007155:Immunologic Factors / Q000008:administration & dosage*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D023421:Models, Animal; D010718:Phosphatidylserines / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology; D013921:Thrombocytopenia / Q000097:blood / Q000628:therapy*
chemical_list: D001323:Autoantibodies; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D010718:Phosphatidylserines; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases