Intravenous immunoglobulin inhibits anti-glycoprotein IIb-induced platelet apoptosis in a murine model of immune thrombocytopenia.
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.
Leytin
Valery
V
Division of Transfusion Medicine, Department of Laboratory Medicine, St Michael's Hospital, Toronto, ON, Canada. leytinv@smh.toronto.on.ca
Mykhaylov
Sergiy
S
Starkey
Alison F
AF
Allen
David J
DJ
Lau
Herbert
H
Ni
Heyu
H
Semple
John W
JW
Lazarus
Alan H
AH
Freedman
John
J
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*
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