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Activation of the P2X7 receptor induces the rapid shedding of CD23 from human and murine B cells

Journal Article


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Abstract


  • Activation of the P2X7 receptor by the extracellular damage-associated molecular pattern, adenosine 5′-triphosphate (ATP), induces the shedding of cell surface molecules including the low-affinity IgE receptor, CD23, from human leukocytes. A disintegrin and metalloprotease (ADAM) 10 mediates P2X7-induced shedding of CD23 from multiple myeloma RPMI 8226 B cells; however, whether this process occurs in primary B cells is unknown. The aim of the current study was to determine whether P2X7 activation induces the rapid shedding of CD23 from primary human and murine B cells. Flow cytometric and ELISA measurements showed that ATP treatment of human and murine B cells induced the rapid shedding of CD23. Treatment of cells with the specific P2X7 antagonist, AZ10606120, near-completely impaired ATP-induced CD23 shedding from both human and murine B cells. ATP-induced CD23 shedding was also impaired in B cells from P2X7 knockout mice. The absence of full-length, functional P2X7 in the P2X7 knockout mice was confirmed by immunoblotting of splenic cells, and by flow cytometric measurements of ATP-induced YO-PRO-12+ uptake into splenic B and T cells. The broad-spectrum metalloprotease antagonist, BB-94, and the ADAM10 antagonist, GI254023X, impaired P2X7-induced CD23 shedding from both human and murine B cells. These data indicate that P2X7 activation induces the rapid shedding of CD23 from primary human and murine B cells and that this process may be mediated by ADAM10.

Publication Date


  • 2015

Citation


  • Pupovac, A., Geraghty, N. J., Watson, D. & Sluyter, R. (2015). Activation of the P2X7 receptor induces the rapid shedding of CD23 from human and murine B cells. Immunology and Cell Biology, 93 (1), 77-85.

Scopus Eid


  • 2-s2.0-84920535295

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3458&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2439

Has Global Citation Frequency


Number Of Pages


  • 8

Start Page


  • 77

End Page


  • 85

Volume


  • 93

Issue


  • 1

Place Of Publication


  • United Kingdom

Abstract


  • Activation of the P2X7 receptor by the extracellular damage-associated molecular pattern, adenosine 5′-triphosphate (ATP), induces the shedding of cell surface molecules including the low-affinity IgE receptor, CD23, from human leukocytes. A disintegrin and metalloprotease (ADAM) 10 mediates P2X7-induced shedding of CD23 from multiple myeloma RPMI 8226 B cells; however, whether this process occurs in primary B cells is unknown. The aim of the current study was to determine whether P2X7 activation induces the rapid shedding of CD23 from primary human and murine B cells. Flow cytometric and ELISA measurements showed that ATP treatment of human and murine B cells induced the rapid shedding of CD23. Treatment of cells with the specific P2X7 antagonist, AZ10606120, near-completely impaired ATP-induced CD23 shedding from both human and murine B cells. ATP-induced CD23 shedding was also impaired in B cells from P2X7 knockout mice. The absence of full-length, functional P2X7 in the P2X7 knockout mice was confirmed by immunoblotting of splenic cells, and by flow cytometric measurements of ATP-induced YO-PRO-12+ uptake into splenic B and T cells. The broad-spectrum metalloprotease antagonist, BB-94, and the ADAM10 antagonist, GI254023X, impaired P2X7-induced CD23 shedding from both human and murine B cells. These data indicate that P2X7 activation induces the rapid shedding of CD23 from primary human and murine B cells and that this process may be mediated by ADAM10.

Publication Date


  • 2015

Citation


  • Pupovac, A., Geraghty, N. J., Watson, D. & Sluyter, R. (2015). Activation of the P2X7 receptor induces the rapid shedding of CD23 from human and murine B cells. Immunology and Cell Biology, 93 (1), 77-85.

Scopus Eid


  • 2-s2.0-84920535295

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=3458&context=smhpapers

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/2439

Has Global Citation Frequency


Number Of Pages


  • 8

Start Page


  • 77

End Page


  • 85

Volume


  • 93

Issue


  • 1

Place Of Publication


  • United Kingdom