title: Involvement of dihydropyridine-sensitive calcium channels in human dendritic cell function. Competition by HIV-1 Tat.
abstract: The entry of extracellular calcium in leukocytes mediates several cellular processes; however, unlike in excitable tissues, the underlying molecular mechanisms are poorly defined. In this paper we provide phenotypical and biochemical evidence that peripheral blood-derived human dendritic cells express dihydropyridine-sensitive calcium channels. Exposure to the dihydropyridine drug nifedipine, which binds L-type calcium channels blocking calcium influx, prevents two dendritic cell functions that are dependent on extracellular calcium entry: apoptotic body engulfment and interleukin-12 production induced by cross-linking of the surface lectin NKRP1A. It is known that exogenous human immunodeficiency virus, type 1 Tat affects several Ca2+-dependent immune cell responses. Here we demonstrate that Tat inhibits apoptotic body engulfment and interleukin-12 production by blocking extracellular calcium influx. This inhibition is prevented by the calcium channel agonist dihydropyridine derivative Bay K 8644, suggesting the involvement of L-type calcium channels. This hypothesis is further supported by the observation that Tat and dihydropyridine drugs compete for binding to dendritic cells. Taken together, these findings indicate that exogenous Tat exerts its inhibitory effects on dendritic cells by blocking dihydropyridine-sensitive L-type calcium channels.
authors.affiliation: Laboratory of Immunopathology, National Institute for Cancer Research and Advanced Biotechnology Center, Genoa 16132, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Poggi
authors.forename: A
authors.initials: A
authors.lastname: Rubartelli
authors.forename: M R
authors.initials: MR
authors.lastname: Zocchi
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000954:Antigens, Surface / Q000494:pharmacology; D017209:Apoptosis; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015696:Gene Products, tat / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000378:metabolism; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D009543:Nifedipine / Q000494:pharmacology; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: D000954:Antigens, Surface; D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D015696:Gene Products, tat; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D054322:tat Gene Products, Human Immunodeficiency Virus; D018664:Interleukin-12; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D002118:Calcium