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The human P2X7 receptor and its role in innate immunity

Journal Article


Abstract


  • The human P2X7 receptor is a two-transmembrane ionotropic receptor which has a

    ubiquitous distribution and is most highly expressed on immune cells. In macrophages

    and similar myeloid cells primed by lipopolysaccharide (LPS), activation of P2X7 by

    extracellular ATP opens a cation channel/pore allowing massive K+ efflux associated

    with processing and secretion of pro-inflammatory cytokines interleukin (IL)-1β

    and IL-18. A variety of other downstream effects follows P2X7 activation over

    several minutes including shedding of certain surface molecules, membrane blebbing,

    microvesicle/exosome release and apoptosis of the cell. High concentrations of ATP

    (>100 μM) are required to activate P2X7 but it remains unclear where these levels

    exist, other than in inflammatory foci or confined spaces such as in bone. A variety

    of potent selective antagonists of P2X7 activation have recently become available,

    allowing clinical trials to be undertaken in inflammatory and immune-mediated

    disorders.

    Proteomic studies have shown that P2X7 exists as a large multiprotein complex

    which includes non-muscle myosin heavy chain and other elements of the cytoskeleton.

    In the absence of its ATP ligand and serum, P2X7 has an alternate function in the

    recognition and phagocytosis of non-opsonized foreign particles, including bacteria

    and apoptotic cells. The P2RX7 gene has many polymorphic variants and isoforms

    which increase or decrease function of the receptor. Genetic association studies have

    linked loss-of-function polymorphisms with reactivation of latent tuberculosis as well

    as symptomatic infection with certain other obligate intracellular pathogens. The many

    roles involving P2X7 suggest that this receptor is essential to fundamental aspects of

    the innate immune response.

Authors


  •   Wiley, James S. (external author)
  •   Sluyter, Ronald
  •   Gu, Ben J. (external author)
  •   Stokes, Leanne (external author)
  •   Fuller, Stephen J. (external author)

Publication Date


  • 2011

Citation


  • Wiley, J. S., Sluyter, R., Gu, B. J., Stokes, L. & Fuller, S. J. (2011). The human P2X7 receptor and its role in innate immunity. Tissue Antigens: immune response genetics, 78 (5), 321-332.

Scopus Eid


  • 2-s2.0-80053898343

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/3894

Number Of Pages


  • 11

Start Page


  • 321

End Page


  • 332

Volume


  • 78

Issue


  • 5

Abstract


  • The human P2X7 receptor is a two-transmembrane ionotropic receptor which has a

    ubiquitous distribution and is most highly expressed on immune cells. In macrophages

    and similar myeloid cells primed by lipopolysaccharide (LPS), activation of P2X7 by

    extracellular ATP opens a cation channel/pore allowing massive K+ efflux associated

    with processing and secretion of pro-inflammatory cytokines interleukin (IL)-1β

    and IL-18. A variety of other downstream effects follows P2X7 activation over

    several minutes including shedding of certain surface molecules, membrane blebbing,

    microvesicle/exosome release and apoptosis of the cell. High concentrations of ATP

    (>100 μM) are required to activate P2X7 but it remains unclear where these levels

    exist, other than in inflammatory foci or confined spaces such as in bone. A variety

    of potent selective antagonists of P2X7 activation have recently become available,

    allowing clinical trials to be undertaken in inflammatory and immune-mediated

    disorders.

    Proteomic studies have shown that P2X7 exists as a large multiprotein complex

    which includes non-muscle myosin heavy chain and other elements of the cytoskeleton.

    In the absence of its ATP ligand and serum, P2X7 has an alternate function in the

    recognition and phagocytosis of non-opsonized foreign particles, including bacteria

    and apoptotic cells. The P2RX7 gene has many polymorphic variants and isoforms

    which increase or decrease function of the receptor. Genetic association studies have

    linked loss-of-function polymorphisms with reactivation of latent tuberculosis as well

    as symptomatic infection with certain other obligate intracellular pathogens. The many

    roles involving P2X7 suggest that this receptor is essential to fundamental aspects of

    the innate immune response.

Authors


  •   Wiley, James S. (external author)
  •   Sluyter, Ronald
  •   Gu, Ben J. (external author)
  •   Stokes, Leanne (external author)
  •   Fuller, Stephen J. (external author)

Publication Date


  • 2011

Citation


  • Wiley, J. S., Sluyter, R., Gu, B. J., Stokes, L. & Fuller, S. J. (2011). The human P2X7 receptor and its role in innate immunity. Tissue Antigens: immune response genetics, 78 (5), 321-332.

Scopus Eid


  • 2-s2.0-80053898343

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/3894

Number Of Pages


  • 11

Start Page


  • 321

End Page


  • 332

Volume


  • 78

Issue


  • 5