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Human P2X7 receptor activation induces ADAM10-mediated shedding of CD23 and CXCL16 (P4137)

Journal Article


Abstract


  • Activation of the damage-associated molecular pattern receptor P2X7 by extracellular ATP induces the shedding of cell surface molecules, including CD23, from leukocytes. The mechanisms involved in this process however remain poorly understood. Using a flow cytometric assay, we demonstrated that ATP-induces the rapid shedding of CD23 from the surface of human multiple myeloma RPMI 8226 and peripheral blood B cells with a t1/2 of 7 min. The P2X7 antagonist, AZ10606120, impaired ATP-induced CD23 shedding by 89%. Moreover, P2X7-induced CD23 shedding was impaired by a broad-spectrum metalloprotease inhibitor, BB-94, by 63% and the ADAM10 inhibitor, GI254023X, by 67%. RT-PCR confirmed the expression of ADAM10 in B cells. P2X7-induced CD23 shedding was not dependent on changes in extracellular Na+, K+ and Ca2+ concentrations, and was unaffected by a panel of enzyme inhibitors targeting various kinases and phospholipases previously implicated in P2X7-mediated signaling events. ATP also induced the rapid shedding of the ADAM10 substrate, CXCL16, with a t1/2 of 1 min. AZ10606120 impaired ATP-induced CXCL16 shedding by 86%. Moreover, P2X7-induced CXCL16 shedding was impaired by BB-94 by 77% and GI254023X by 87%. This data indicates that human P2X7 activation induces the rapid shedding of CD23 and CXCL16, and that this process involves ADAM10. Thus, P2X7 may represent a novel target in disorders involving CD23 or CXCL16.

Authors


  •   Pupovac, Aleta (external author)
  •   Wang, Bin (external author)
  •   Foster, Christopher M. (external author)
  •   Sluyter, Ronald

Publication Date


  • 2013

Citation


  • Pupovac, A., Wang, B., Foster, C. & Sluyter, R. (2013). Human P2X7 receptor activation induces ADAM10-mediated shedding of CD23 and CXCL16 (P4137). Journal of Immunology, 190 (Meeting Abstract Suppl.), 112.2-112.2.

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/1101

Start Page


  • 112.2

End Page


  • 112.2

Volume


  • 190

Issue


  • Meeting Abstract Suppl.

Place Of Publication


  • http://jimmunol.org/cgi/content/meeting_abstract/190/1_MeetingAbstracts/112.2

Abstract


  • Activation of the damage-associated molecular pattern receptor P2X7 by extracellular ATP induces the shedding of cell surface molecules, including CD23, from leukocytes. The mechanisms involved in this process however remain poorly understood. Using a flow cytometric assay, we demonstrated that ATP-induces the rapid shedding of CD23 from the surface of human multiple myeloma RPMI 8226 and peripheral blood B cells with a t1/2 of 7 min. The P2X7 antagonist, AZ10606120, impaired ATP-induced CD23 shedding by 89%. Moreover, P2X7-induced CD23 shedding was impaired by a broad-spectrum metalloprotease inhibitor, BB-94, by 63% and the ADAM10 inhibitor, GI254023X, by 67%. RT-PCR confirmed the expression of ADAM10 in B cells. P2X7-induced CD23 shedding was not dependent on changes in extracellular Na+, K+ and Ca2+ concentrations, and was unaffected by a panel of enzyme inhibitors targeting various kinases and phospholipases previously implicated in P2X7-mediated signaling events. ATP also induced the rapid shedding of the ADAM10 substrate, CXCL16, with a t1/2 of 1 min. AZ10606120 impaired ATP-induced CXCL16 shedding by 86%. Moreover, P2X7-induced CXCL16 shedding was impaired by BB-94 by 77% and GI254023X by 87%. This data indicates that human P2X7 activation induces the rapid shedding of CD23 and CXCL16, and that this process involves ADAM10. Thus, P2X7 may represent a novel target in disorders involving CD23 or CXCL16.

Authors


  •   Pupovac, Aleta (external author)
  •   Wang, Bin (external author)
  •   Foster, Christopher M. (external author)
  •   Sluyter, Ronald

Publication Date


  • 2013

Citation


  • Pupovac, A., Wang, B., Foster, C. & Sluyter, R. (2013). Human P2X7 receptor activation induces ADAM10-mediated shedding of CD23 and CXCL16 (P4137). Journal of Immunology, 190 (Meeting Abstract Suppl.), 112.2-112.2.

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/1101

Start Page


  • 112.2

End Page


  • 112.2

Volume


  • 190

Issue


  • Meeting Abstract Suppl.

Place Of Publication


  • http://jimmunol.org/cgi/content/meeting_abstract/190/1_MeetingAbstracts/112.2