title: S100A9 deficiency alters adenosine-5'-triphosphate induced calcium signalling but does not generally interfere with calcium and zinc homeostasis in murine neutrophils.
abstract: The two calcium- and zinc-binding proteins, S100A9 and S100 A8, abundant in myeloid cells are considered to play important roles in both calcium signalling and zinc homeostasis. Polymorphonuclear neutrophils from S100A9 ko mice are also devoid of S100A8. Therefore, S100A9-deficient neutrophils were used as a model to study the role of the two S100 proteins in the neutrophils's calcium and zinc metabolism. Analysis of the intracellular zinc level upon pyrithione and (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexeneamide (NOR-1) treatment revealed no differences between S100A9-deficient and wildtype neutrophils. Similar, the calcium signals were not distinguishable from S100A9-deficient and wildtype neutrophils upon stimulation with platelet activating factor (PAF), thapsigargin or macrophage inflammatory protein 1 alpha (MIP-1 alpha), indicating despite their massive expression S100A8/A9 do neither serve as calcium nor as zinc buffering proteins in granulocytes. In contrast, stimulation with adenosine-5'-triphosphate (ATP) induces a significant stronger increase of the intracellular free calcium level in S100A9-deficient cells compared to wildtype cells. Moreover, the ATP-induced calcium signal was still different when the cells were incubated in calcium free buffer suggesting that pirinergic receptors of the P(2Y) class could be involved in this signalling pathway.
authors.affiliation: Institute of Experimental Dermatology, University of Münster, Röntgenstr. 21, D-48149 Münster, Germany. nacken@uni-muenster.de
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Nacken
authors.forename: Frank C
authors.initials: FC
authors.lastname: Mooren
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Manitz
authors.forename: Günther
authors.initials: G
authors.lastname: Bode
authors.forename: Clemens
authors.initials: C
authors.lastname: Sorg
authors.forename: Claus
authors.initials: C
authors.lastname: Kerkhoff
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D040501:Calgranulin A / Q000502:physiology*; D040502:Calgranulin B / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D004591:Electrophoresis, Polyacrylamide Gel; D006706:Homeostasis / Q000187:drug effects; D006898:Hydroxylamines / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010972:Platelet Activating Factor / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects; D013871:Thiones; D014105:Tosyl Compounds / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism*
chemical_list: C477506:(+-)-E-4-methyl-2-((E)-hydroxylamino)-5-nitro-6-methoxy-3-hexanamide; D040501:Calgranulin A; D040502:Calgranulin B; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D006898:Hydroxylamines; D019402:Macrophage Inflammatory Proteins; D010972:Platelet Activating Factor; D011725:Pyridines; D015363:Quinolones; D013871:Thiones; D014105:Tosyl Compounds; C008704:pyrithione; D000255:Adenosine Triphosphate; D015032:Zinc; D002118:Calcium; C084731:zinquin