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Human P2Y11 Expression Level Affects Human P2X7 Receptor-Mediated Cell Death

Karin Dreisig1, Louise Sund1, Maja Wallentin Dommer1

  • 1Molecular Sleep Laboratory, Department of Clinical Biochemistry, Rigshospitalet, Glostrup Hospital, Glostrup, Denmark.

Frontiers in Immunology
|June 26, 2018
PubMed

Insights

High extracellular adenosine triphosphate (ATP) causes T lymphocyte cell death. In humans, the P2Y11 receptor, not P2X7 receptor expression, influences this ATP-induced cell death, revealing a species-specific mechanism.

Area of Science:

  • Immunology
  • Cell Biology
  • Pharmacology

Background:

  • Extracellular adenosine triphosphate (ATP) at high concentrations induces T lymphocyte cell death.
  • In mice, differential P2X7 receptor expression explains the varied response of CD4+ and CD8+ T lymphocytes to ATP.
  • The mechanism underlying differential T lymphocyte responses to ATP analogs in humans is not fully understood.

Purpose of the Study:

  • To investigate the differential response of human CD4+ and CD8+ T lymphocytes to the synthetic ATP analog, BzATP.
  • To elucidate the role of P2X7 and P2Y11 receptors in BzATP-induced T lymphocyte cell death in humans.
  • To identify species-specific differences in ATP-mediated T lymphocyte cell death mechanisms.

Main Methods:

  • Compared human CD4+ and CD8+ T lymphocyte responses to BzATP.
  • Assessed P2X7 and P2Y11 receptor expression levels in human lymphocytes.
  • Utilized a recombinant expression system to study receptor interactions and BzATP-induced cell death markers (lactate dehydrogenase release, pore formation).

Main Results:

  • Human T lymphocyte response to BzATP was not solely dependent on P2X7 receptor expression levels.
  • BzATP-induced P2X7 receptor response correlated with P2Y11 receptor expression in human lymphocyte subtypes.
  • Co-expression of P2Y11 receptor counteracted BzATP-induced P2X7 receptor-mediated cell death and pore formation, independent of calcium signaling.

Conclusions:

  • Significant species differences exist in ATP-mediated T lymphocyte cell death between mice and humans.
  • In human T lymphocytes, P2Y11 receptor expression is a key factor correlating with P2X7 receptor-driven cell death following BzATP stimulation.
  • P2Y11 receptor's inhibitory effect on P2X7 receptor function is independent of its signaling pathway.
Keywords:
A740003Fluo-4P2RX7P2RY11YO-PRO-1cyclic adenosine monophosphatepurinergic

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