Inhibition of macrophage secretion by tetanus toxin is not directly linked to cytosolic calcium homeostasis.
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.
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
D000634:Aminoquinolines; D004987:Ethers; D013744:Tetanus Toxin; D015759:Ionomycin; C035738:Quin2-acetoxymethyl ester; D009113:Muramidase; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium