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Artículo

Platelet Apoptosis in Adult Immune Thrombocytopenia: Insights into the Mechanism of Damage Triggered by Auto-antibodies

Goette, Nora PaulaIcon ; Glembotsky, Ana ClaudiaIcon ; Lev, Paola RoxanaIcon ; Grodzielski, MatíasIcon ; Contrufo, Geraldine; Pierdominici, Marta S.; Espasandin, Yesica RominaIcon ; Riveros, Dardo Alberto; García, Alejandro Jorge; Molinas, Felisa ConcepciónIcon ; Heller, Paula GracielaIcon ; Marta, Rosana FernandaIcon
Fecha de publicación: 08/2016
Editorial: Public Library of Science
Revista: Plos One
ISSN: 1932-6203
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Bioquímica y Biología Molecular

Resumen

Mechanisms leading to decreased platelet count in immune thrombocytopenia (ITP) are heterogeneous. This study describes increased platelet apoptosis involving loss of mitochondrial membrane potential (ΔΨm), caspase 3 activation (aCasp3) and phosphatidylserine (PS) externalization in a cohort of adult ITP patients. Apoptosis was not related to platelet activation, as PAC-1 binding, P-selectin exposure and GPIb-IX internalization were not increased. Besides, ITP platelets were more sensitive to apoptotic stimulus in terms of aCasp3. Incubation of normal platelets with ITP plasma induced loss of ΔΨm, while PS exposure and aCasp3 remained unaltered. The increase in PS exposure observed in ITP platelets could be reproduced in normal platelets incubated with ITP plasma by adding normal CD3+ lymphocytes to the system as effector cells. Addition of leupeptin -a cathepsin B inhibitor- to this system protected platelets from apoptosis. Increased PS exposure was also observed when normal platelets and CD3+ lymphocytes were incubated with purified IgG from ITP patients and was absent when ITP plasma was depleted of auto-antibodies, pointing to the latter as responsible for platelet damage. Apoptosis was present in platelets from all patients carrying anti-GPIIb-IIIa and anti-GPIb auto-antibodies but was absent in the patient with anti-GPIa-IIa auto-antibodies. Platelet damage inversely correlated with platelet count and decreased during treatment with a thrombopoietin receptor agonist. These results point to a key role for auto-antibodies in platelet apoptosis and suggest that antibody-dependent cell cytotoxicity is the mechanism underlying this phenomenon.
Palabras clave: Auto-Antibodies , Platelets , Apoptosis , Immune Thobocytopenia , Cd3+ Lymphocytes
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/43828
DOI: http://dx.doi.org/10.1371/journal.pone.0160563
URL: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0160563
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Articulos(IDIM)
Articulos de INST.DE INVEST.MEDICAS
Citación
Goette, Nora Paula; Glembotsky, Ana Claudia; Lev, Paola Roxana; Grodzielski, Matías; Contrufo, Geraldine; et al.; Platelet Apoptosis in Adult Immune Thrombocytopenia: Insights into the Mechanism of Damage Triggered by Auto-antibodies; Public Library of Science; Plos One; 11; 8; 8-2016; 1-14; e0160563
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