title: Human epidermal and monocyte-derived langerhans cells express functional P2X receptors.
abstract: Monocyte-derived dendritic cells (Mo-DC) express functional P2X7 receptors; however, the expression of these receptors on tissue-derived dendritic cells including epidermal Langerhans cells (LC) is unknown. Using immunolabeling and flow cytometry, we demonstrated that P2X7 was present on both human epidermal LC and monocyte-derived LC (Mo-LC), as well as on human keratinocytes. The ecto-ATPDase (CD39) was also present on LC, but not keratinocytes. The P2X7 agonists, 2'- and 3'-0(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP) or ATP, but neither adenosine 5'-diphosphate (ADP) nor uridine 5'-triphosphate (UTP), induced ethidium+ uptake into these cells. Furthermore, ATP-induced ethidium+ uptake into epidermal LC, Mo-LC and keratinocytes was inhibited by the specific P2X7 antagonist, KN-62 (1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine). ATP-induced ethidium+ uptake into Mo-LC and Mo-DC was 2- and 3-fold greater, respectively, than that for fresh monocytes. P2X7 activation on LC induced downstream signaling events, as BzATP or ATP, but neither ADP nor UTP, induced shedding of the low-affinity receptor for IgE (CD23) from Mo-LC. This process was inhibited by KN-62. Finally, ATP-induced ethidium+ uptake and CD23 shedding were impaired in Mo-LC obtained from subjects homozygous for the loss-of-function Glu-496 to Ala polymorphism in the P2X7 receptor. These results demonstrate that human LC express functional P2X7 receptors, and suggest a role for this receptor in the skin immune system.
authors.affiliation: Department of Medicine, University of Sydney at Nepean Hospital, Penrith, NSW, Australia.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Georgiou
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Skarratt
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Fuller
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Martin
authors.forename: Richard I
authors.initials: RI
authors.lastname: Christopherson
authors.forename: James S
authors.initials: JS
authors.lastname: Wiley
authors.forename: Ronald
authors.initials: R
authors.lastname: Sluyter
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D000078404:Epidermal Cells; D004996:Ethidium / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D007801:Langerhans Cells / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology*; D011110:Polymorphism, Genetic; D017455:Receptors, IgE / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D012867:Skin / Q000276:immunology
chemical_list: C546468:P2RX7 protein, human; D017455:Receptors, IgE; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000255:Adenosine Triphosphate; D004996:Ethidium