title: Receptor-activated calcium influx in human monocytes exposed to monocyte chemotactic protein-1 and related cytokines.
abstract: Stimulation of human monocytes with monocyte chemotactic protein-1 (MCP-1) resulted in an increase of [Ca2+]i. The [Ca2+]i rise was dependent on external Ca2+, could be reconstituted by the addition of external Ca2+ and was blocked by Ni2+. Agonist-stimulated Ca2+ influx was demonstrated directly by the use of Mn2+: in the presence of extracellular Mn2+, MCP-1 and FMLP stimulated a dose-dependent quench in fluorescence of Fura-2-loaded monocytes. This quench was the result of stimulation of Mn2+ influx and was blocked by Ni2+ and by the Ca2+ channel inhibitor SC38249. Pretreatment of monocytes with verapamil and nifedipine or high depolarizing [K+] had no effect. MCP-1 did not induce production of inositol triphosphate nor turnover of phosphatidylinositol 4,5-biphosphate. Collectively, these results show that MCP-1 does not induce discharge of intracellular stores. This chemokine stimulates divalent cation entry (Ca2+ or Mn2+) by a mechanism independent of changes in [Ca2+]i, unrelated to voltage-dependent Ca2+ channels and presumably involving receptor-activated channels. In addition to MCP-1, also two other members of the chemokine Cys-Cys family, RANTES and MIP-1 alpha, stimulated [Ca2+]i increase. Exposure of human monocytes to either RANTES or MIP-1 alpha, had no effect on a subsequent stimulation by MCP-1. On the contrary, MCP-1 cross-desensitized monocytes for a subsequent stimulation with RANTES and MIP-1 alpha. These results suggest a certain level of receptor sharing among members of the Cys-Cys chemokine family.
authors.affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Sozzani
authors.forename: M
authors.initials: M
authors.lastname: Molino
authors.forename: M
authors.initials: M
authors.lastname: Locati
authors.forename: W
authors.initials: W
authors.lastname: Luini
authors.forename: C
authors.initials: C
authors.lastname: Cerletti
authors.forename: A
authors.initials: A
authors.lastname: Vecchi
authors.forename: A
authors.initials: A
authors.lastname: Mantovani
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D002630:Chemotactic Factors / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008222:Lymphokines / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins; D008345:Manganese / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D015846:Monokines / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D002630:Chemotactic Factors; D016207:Cytokines; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011994:Recombinant Proteins; D005576:Colforsin; D008345:Manganese; D015544:Inositol 1,4,5-Trisphosphate; D014700:Verapamil; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium