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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02074

Human peripheral blood eosinophils express high level of the purinergic receptor P2X4

Viiu Paalme1*, Airi Rump1, Kati Mädo2, Marina Teras2, Birgit Truumees2,  Helen Aitai1,  Kristel Ratas1,  Mickael Bourge3,  Chi-Shiun Chiang4, Aram Ghalali5, thierry tordjmann6, Juri Teras7,  Pierre Boudinot8,  Jean M. Kanellopoulos6 and  Sirje Rüütel Boudinot1*
  • 1Tallinn University of Technology, Estonia
  • 2North Estonia Medical Centre, Estonia
  • 3Institute for Integrative Biology of the Cell, Délégation Ile-de-France Sud (CNRS), France
  • 4National Tsing Hua University, Taiwan
  • 5Karolinska Institute (KI), Sweden
  • 6Université Paris-Sud, France
  • 7Department of Oncology, North Estonia Medical Centre, Estonia
  • 8INRA Centre Jouy-en-Josas, France

Extracellular nucleotides are important mediators of cell activation and trigger multiple responses via membrane receptors known as purinergic receptors (P2). P2X receptors are ligand-gated ion channels, activated by extracellular ATP. P2X4 is one of the most sensitive purinergic receptors, that is typically expressed by neurons, microglia, and some epithelial and endothelial cells. P2X4 mediates neuropathic pain via brain-derived neurotrophic factor and is also involved in inflammation in response to high ATP release. It is therefore involved in multiple inflammatory pathologies as well as neurodegenerative diseases. We have produced monoclonal antibodies (mAb) directed against this important human P2X4 receptor. Focusing on two mAbs, we showed that they also recognize mouse and rat P2X4. We demonstrated that these mAbs can be used in flow cytometry, immunoprecipitation and immunohistochemistry, but not in Western blot assays, indicating that they target conformational epitopes. We also characterised the expression of P2X4 receptor on mouse and human peripheral blood lymphocytes (PBL). We showed that P2X4 is expressed at the surface of several leukocyte cell types, with the highest expression level on eosinophils, making them potentially sensitive to adenosine triphosphate (ATP). P2X4 is expressed by leucocytes, in human and mouse, with a significant gender difference, males having higher surface expression levels than females. Our findings reveal that PBL express significant levels of P2X4 receptor, and suggest an important role of this receptor in leukocyte activation by ATP, particularly in P2X4high expressing eosinophils.

Keywords: P2X4 purinergic receptor, Monoclonal antibody, Eosinophils, PBL marker, sex difference

Received: 30 Dec 2018; Accepted: 16 Aug 2019.

Copyright: © 2019 Paalme, Rump, Mädo, Teras, Truumees, Aitai, Ratas, Bourge, Chiang, Ghalali, tordjmann, Teras, Boudinot, Kanellopoulos and Rüütel Boudinot. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Mrs. Viiu Paalme, Tallinn University of Technology, Tallinn, 19086, Harju County, Estonia, viiu.paalme@gmail.com
Dr. Sirje Rüütel Boudinot, Tallinn University of Technology, Tallinn, 19086, Harju County, Estonia, sirje.boudinot@gmail.com