Skip to main content
Log in

Imbalanced expression of Bcl-xL and Bax in platelets treated with plasma from immune thrombocytopenia

  • Original Article
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Immune thrombocytopenia is a heterogeneous autoimmune disease, characterized by accelerated platelet destruction and impaired platelet production. Bcl-xL and Bax play an opposite role in the regulation of apoptotic process with Bcl-xL for cell survival and Bax for cell apoptosis. Given the critical roles in the regulation of platelet apoptosis, whether Bcl-xL or Bax was involved in the pathogenesis of ITP remains unknown. The aim of this study is to evaluate the expression profile of Bcl-xL and Bax in platelets treated with ITP plasma. Normal washed platelets were treated with plasma from 20 active ITP patients or 10 age and gender-matched control to mimic the ITP in vivo environment. Mitochondrial depolarization, platelet apoptosis and activation were measured by flow cytometry. Expression of Bcl-xL, Bax and caspase-3 were also measured by quantitative real-time PCR and western blot. Our results demonstrated increased mitochondrial depolarization, platelet apoptosis and activation in platelets after treated with ITP plasma in comparison to control. In addition, decreased expression of Bcl-xL, increased expression of Bax and activity of caspase-3 were also observed. Furthermore, a negative correlation of Bcl-xL with Bax was found in platelets treated with ITP plasma. In conclusion, imbalanced expression of Bcl-xL and Bax might be associated with platelet apoptosis in ITP and therapeutically targeting them might be a novel approach in the treatment of ITP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Neunert CE. Current management of immune thrombocytopenia. Hematol Am Soc Hematol Educ Progr. 2013;2013:276–82.

    Article  Google Scholar 

  2. Cines DB, Cuker A, Semple JW. Pathogenesis of immune thrombocytopenia. Presse Med. 2014;43:e49–59.

    Article  PubMed  Google Scholar 

  3. McKenzie CG, Guo L, Freedman J, Semple JW. Cellular immune dysfunction in immune thrombocytopenia (ITP). Br J Haematol. 2013;163:10–23.

    Article  CAS  PubMed  Google Scholar 

  4. Chow L, Aslam R, Speck ER, Kim M, Cridland N, Webster ML, et al. A murine model of severe immune thrombocytopenia is induced by antibody- and CD8+ T cell-mediated responses that are differentially sensitive to therapy. Blood. 2010;115:1247–53.

    Article  CAS  PubMed  Google Scholar 

  5. Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115:168–86.

    Article  CAS  PubMed  Google Scholar 

  6. von Gunten S, Wehrli M, Simon HU. Cell death in immune thrombocytopenia: novel insights and perspectives. Semin Hematol. 2013;50(Suppl 1):S109–15.

    Article  Google Scholar 

  7. Mason KD, Carpinelli MR, Fletcher JI, Collinge JE, Hilton AA, Ellis S, et al. Programmed anuclear cell death delimits platelet life span. Cell. 2007;128:1173–86.

    Article  CAS  PubMed  Google Scholar 

  8. White MJ, Kile BT. Apoptotic processes in megakaryocytes and platelets. Semin Hematol. 2010;47:227–34.

    Article  CAS  PubMed  Google Scholar 

  9. Qi B, Hardwick JM. A Bcl-xL timer sets platelet life span. Cell. 2007;128:1035–6.

    Article  CAS  PubMed  Google Scholar 

  10. Schoenwaelder SM, Jarman KE, Gardiner EE, Hua M, Qiao J, White MJ, et al. Bcl-xL-inhibitory BH3 mimetics can induce a transient thrombocytopathy that undermines the hemostatic function of platelets. Blood. 2011;118:1663–74.

    Article  CAS  PubMed  Google Scholar 

  11. Qiao J, Liu Y, Li X, Xia Y, Wu Y, Li D, et al. Elevated expression of NLRP3 in patients with immune thrombocytopenia. Immunol Res 2015.

  12. Qiao J, Liu Y, Wu Y, Li X, Zhu F, Xia Y, et al. Aberrant expression of RUNX3 in patients with immune thrombocytopenia. Int Immunopharmacol. 2015;28:252–6.

    Article  CAS  PubMed  Google Scholar 

  13. Billen LP, Kokoski CL, Lovell JF, Leber B, Andrews DW. Bcl-XL inhibits membrane permeabilization by competing with Bax. PLoS Biol. 2008;6:e147.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Ghavami S, Hashemi M, Ande SR, Yeganeh B, Xiao W, Eshraghi M, et al. Apoptosis and cancer: mutations within caspase genes. J Med Genet. 2009;46:497–510.

    Article  CAS  PubMed  Google Scholar 

  15. Porter AG, Janicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999;6:99–104.

    Article  CAS  PubMed  Google Scholar 

  16. Walters J, Pop C, Scott FL, Drag M, Swartz P, Mattos C, et al. A constitutively active and uninhibitable caspase-3 zymogen efficiently induces apoptosis. Biochem J. 2009;424:335–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Semple JW, Italiano JE Jr, Freedman J. Platelets and the immune continuum. Nat Rev Immunol. 2011;11:264–74.

    Article  CAS  PubMed  Google Scholar 

  18. Leytin V. Apoptosis in the anucleate platelet. Blood Rev. 2012;26:51–63.

    Article  CAS  PubMed  Google Scholar 

  19. Leytin V, Allen DJ, Lyubimov E, Freedman J. Higher thrombin concentrations are required to induce platelet apoptosis than to induce platelet activation. Br J Haematol. 2007;136:762–4.

    Article  CAS  PubMed  Google Scholar 

  20. Leytin V, Allen DJ, Mykhaylov S, Mis L, Lyubimov EV, Garvey B, et al. Pathologic high shear stress induces apoptosis events in human platelets. Biochem Biophys Res Commun. 2004;320:303–10.

    Article  CAS  PubMed  Google Scholar 

  21. Leytin V, Allen DJ, Mutlu A, Mykhaylov S, Lyubimov E, Freedman J. Platelet activation and apoptosis are different phenomena: evidence from the sequential dynamics and the magnitude of responses during platelet storage. Br J Haematol. 2008;142:494–7.

    Article  PubMed  Google Scholar 

  22. Savill J, Fadok V. Corpse clearance defines the meaning of cell death. Nature. 2000;407:784–8.

    Article  CAS  PubMed  Google Scholar 

  23. Erwig LP, Henson PM. Clearance of apoptotic cells by phagocytes. Cell Death Differ. 2008;15:243–50.

    Article  CAS  PubMed  Google Scholar 

  24. Heemskerk JW, Bevers EM, Lindhout T. Platelet activation and blood coagulation. Thromb Haemost. 2002;88:186–93.

    CAS  PubMed  Google Scholar 

  25. Catani L, Fagioli ME, Tazzari PL, Ricci F, Curti A, Rovito M, et al. Dendritic cells of immune thrombocytopenic purpura (ITP) show increased capacity to present apoptotic platelets to T lymphocytes. Exp Hematol. 2006;34:879–87.

    Article  CAS  PubMed  Google Scholar 

  26. Winkler J, Kroiss S, Rand ML, Azzouzi I, Annie Bang KW, Speer O, et al. Platelet apoptosis in paediatric immune thrombocytopenia is ameliorated by intravenous immunoglobulin. Br J Haematol. 2012;156:508–15.

    Article  CAS  PubMed  Google Scholar 

  27. Volkmann N, Marassi FM, Newmeyer DD, Hanein D. The rheostat in the membrane: BCL-2 family proteins and apoptosis. Cell Death Differ. 2014;21:206–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This research was supported by National Natural Science Foundation of China (Grant Nos. 81400082 and 81370602), the Natural Science Foundation of Jiangsu Province (Grant Nos. BK20140219 and BK2012573) and China Postdoctoral Science Foundation funded project (Project No. 2015M570479).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Kailin Xu or Lingyu Zeng.

Ethics declarations

Conflict of interest

The authors have no conflict of interest to declare.

Additional information

Jianlin Qiao and Yun Liu have contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Qiao, J., Liu, Y., Li, D. et al. Imbalanced expression of Bcl-xL and Bax in platelets treated with plasma from immune thrombocytopenia. Immunol Res 64, 604–609 (2016). https://doi.org/10.1007/s12026-015-8760-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-015-8760-z

Keywords

Navigation