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The P2 purinergic receptors of human dendritic cells: identification and coupling to cytokine release
Author(s) -
Ferrari Davide,
La Sala Andrea,
Chiozzi Paola,
Morelli Anna,
Falzoni Simonetta,
Girolomoni Giampiero,
Idzko Marco,
Dichmann Stefan,
Norgauer Johannes,
Di Virgilio Francesco
Publication year - 2000
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0031com
Subject(s) - purinergic receptor , depolarization , p2y receptor , microbiology and biotechnology , lucifer yellow , receptor , p2 receptor , intracellular , agonist , chemistry , membrane potential , stimulation , biophysics , extracellular , biology , biochemistry , endocrinology , gap junction
We investigated the expression of purinoceptors in human dendritic cells, providing functional, pharmacological, and biochemical evidence that immature and mature cells express P2Y and P2X subtypes, coupled to increase in the intracellular Ca 2+ , membrane depolarization, and secretion of inflammatory cytokines. The ATP‐activated Ca 2+ change was biphasic, with a fast release from intracellular stores and a delayed influx across the plasma membrane. A prolonged exposure to ATP was toxic to dendritic cells that swelled, lost typical dendrites, became phase lucent, detached from the substrate, and eventually died. These changes were highly suggestive of expression of the cytotoxic receptor P2X 7 , as confirmed by ability of dendritic cells to become permeant to membrane impermeant dyes such as Lucifer yellow or ethidium bromide. The P2X 7 receptor ligand 2′,3′‐(4‐benzoylbenzoyl)‐ATP was a better agonist then ATP for Ca 2+ increase and plasma membrane depolarization. Oxidized ATP, a covalent blocker of P2X receptors, and the selective P2X 7 antagonist KN‐62 inhibited both permeabilization and Ca 2+ changes induced by ATP. The following purinoceptors were expressed by immature and mature dendritic cells: P2Y 1 , P2Y 2 , P2Y 5 , P2Y 11 and P2X 1 , P2X 4 , P2X 7 . Finally, stimulation of LPS‐matured cells with ATP triggered release of IL‐1 β and TNF‐a. Purinoceptors may provide a new avenue to modulation of dendritic cells function.—Ferrari, D., La Sala, A., Chiozzi, P., Morelli, A., Falzoni, S., Girolomoni, G., Idzko, M., Dichmann, S., Norgauer, J., Di Virgilio, F. The P2 purinergic receptors of human dendritic cells: identification and coupling to cytokine release. FASEB J. 14, 2466–2476 (2000)