Human Peripheral Blood Eosinophils Express High Levels of the Purinergic Receptor P2X4

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...

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Published in:	Frontiers in immunology Vol. 10; p. 2074
Main Authors:	Paalme, Viiu, Rump, Airi, Mädo, Kati, Teras, Marina, Truumees, Birgit, Aitai, Helen, Ratas, Kristel, Bourge, Mickael, Chiang, Chi-Shiun, Ghalali, Aram, Tordjmann, Thierry, Teras, Jüri, Boudinot, Pierre, Kanellopoulos, Jean M, Rüütel Boudinot, Sirje
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers 2019 Frontiers Media S.A
Subjects:	eosinophils gender difference Immunology Life Sciences Medicin och hälsovetenskap monoclonal antibody P2X4 purinergic receptor PBL marker eosinophils gender difference monoclonal antibody P2X4 purinergic receptor PBL marker Monoclonal antibody sex difference Eosinophils
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Summary:	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 characterized 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 P2X4 expressing eosinophils.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Paige Lacy, University of Alberta, Canada Reviewed by: Patricia C. Fulkerson, Cincinnati Children's Hospital Medical Center, United States; Liana Asatryan, University of Southern California, United States This article was submitted to Molecular Innate Immunity, a section of the journal Frontiers in Immunology These authors have contributed equally to this work
ISSN:	1664-3224 1664-3224
DOI:	10.3389/fimmu.2019.02074