title: Inhibition of macrophage secretion by tetanus toxin is not directly linked to cytosolic calcium homeostasis.
abstract: Tetanus toxin (TT) inhibits secretion of neurotransmitters from neurons and lysozyme from human macrophages (Mphi). Because these secretory events are associated with changes in cytosolic free calcium [Ca2+]i, we examined the effect of TT on Mphi calcium homeostasis and secretion in response to ionomycin and phorbol myristate acetate (PMA). Using Quin 2 to report [Ca2+]i, basal [Ca2]i was similar for control cells (133 nM) and Mphi treated with TT (127 nM). In response to ionomycin (50 nM) [Ca2+]i increased to 548 +/- 74 nM in control cells and to 357 +/- 36 nM in TT-treated Mphi (p less than 0.02, N = 12). Despite this rise in [Ca2+]i, neither control Mphi nor TT-treated Mphis secreted the lysosomal enzyme lysozyme in response to this concentration of ionomycin (50 nM). In both control and TT-treated Mphi, stimulation with a higher concentration of ionomycin (1000 nM) caused saturation of the quin 2 fluorescence signal. However, lysozyme secretion from TT-Mphi was inhibited. In response to the phorbol ester, PMA (3 uM), [Ca2+]i did not increase in either control Mphi or TT-treated Mphi. However, secretion of lysozyme from TT-treated Mphi was also inhibited in response to this stimulus (70.8% of control, p less than 0.02, N = 3). These data indicate that the ability of TT to inhibit secretion from Mphi is not directly linked to alterations of cytosolic calcium homeostasis.
mesh_terms: D000634:Aminoquinolines; D002118:Calcium / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000494:pharmacology; D006706:Homeostasis; D006801:Humans; D066298:In Vitro Techniques; D015759:Ionomycin; D008247:Lysosomes / Q000502:physiology; D008264:Macrophages / Q000502:physiology*; D009113:Muramidase / Q000378:metabolism; D013744:Tetanus Toxin / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000634:Aminoquinolines; D004987:Ethers; D013744:Tetanus Toxin; D015759:Ionomycin; C035738:Quin2-acetoxymethyl ester; D009113:Muramidase; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium