The P2 purinergic receptors of human dendritic cells: Identification and coupling to cytokine release

D. Ferrari, A. La Sala, P. Chiozzi, A. Morelli, S. Falzoni, G. Girolomoni, M. Idzko, S. Dichmann, J. Norgauer, F. Di Virgilio

Research output: Contribution to journalArticle

Abstract

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 Ca2+, membrane depolarization, and secretion of inflammatory cytokines. The ATP-activated Ca2+ 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 P2X7, as confirmed by ability of dendritic cells to become permeant to membrane impermeant dyes such as Lucifer yellow or ethidium bromide. The P2X7 receptor ligand 2',3'-(4-benzoylbenzoyl)-ATP was a better agonist then ATP for Ca2+ increase and plasma membrane depolarization. Oxidized ATP, a covalent blocker of P2X receptors, and the selective P2X7, antagonist KN-62 inhibited both permeabilization and Ca2+ changes induced by ATP. The following purinoceptors were expressed by immature and mature dendritic cells: P2Y1, P2Y2, P2Y5, P2Y11 and P2X1, P2X4, P2X7. Finally, stimulation of LPS-matured cells with ATP triggered release of IL-1β and TNF-α. Purinoceptors may provide a new avenue to modulation of dendritic cells function.

Original languageEnglish
Pages (from-to)2466-2476
Number of pages11
JournalFASEB Journal
Volume14
Issue number15
Publication statusPublished - 2000

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Keywords

  • Extracellular nucleotides
  • IL-1β
  • Inflammation
  • Nucleotide receptors
  • TNF-α

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Ferrari, D., La Sala, A., Chiozzi, P., Morelli, A., Falzoni, S., Girolomoni, G., Idzko, M., Dichmann, S., Norgauer, J., & Di Virgilio, F. (2000). The P2 purinergic receptors of human dendritic cells: Identification and coupling to cytokine release. FASEB Journal, 14(15), 2466-2476.