title: Taurine chloramine inhibits functional responses of human eosinophils in vitro.
abstract: BACKGROUND
  Eosinophils are prominent effectors of allergic inflammation. Taurine-chloramine (TauCl), a derivative of the amino acid taurine, shows antioxidant properties in different cell systems but its effects on eosinophils have not been reported.
  
  
  OBJECTIVE
  To study the effects of TauCl and taurine on functional responses of isolated human eosinophils activated by different stimuli.
  
  
  METHODS
  Human eosinophils were purified from the blood of healthy donors by a magnetic bead separation system. The effects of TauCl and taurine (0.1-1 mM) were investigated on the generation of superoxide anion (ferricytochrome-c reduction microassay), calcium signal (fluorimetry), p47phox-p67phox translocation (Western blot), leukotriene C4 (LTC4) production (enzymeimmunoassay), eosinophil peroxidase (EPO) release (spectrophotometry), eosinophil cationic protein (ECP) release (radioimmunoassay), apoptosis (flow cytometry with annexin V-propidium iodide), and nuclear factor-kappaB (NF-kappaB) activation (Western blot).
  
  
  RESULTS
  TauCl inhibited superoxide anion generation triggered by N-formyl-Met-Leu-Phe (fMLP; 30 nM), phorbol myristate acetate (1 nM) and serum opsonized zymosan (0.5 mg/mL) with similar potency (IC50 approximately 200 microM) for the three stimuli, while taurine (0.1-1 mM) was scarcely effective. TauCl but not taurine inhibited p47phox-p67phox translocation. TauCl (200 microM) and taurine (1 mM) did not modify the [Ca2+]i responses to fMLP. TauCl inhibited the release of EPO (IC50 approximately 200 microM) and reduced ECP and LTC4 production from fMLP-activated eosinophils while taurine was without significant effects. TauCl (1 mM) did not change constitutive apoptosis but significantly attenuated the ability of granulocyte-monocyte colony-stimulating factor (GM-CSF) and IL-5 to prevent apoptosis. The activation of eosinophil NF-kappaB induced by GM-CSF and IL-5 was suppressed by TauCl.
  
  
  CONCLUSIONS
  Taurine is without significant in vitro effects on human eosinophil functions but its derivative TauCl inhibits oxidative burst and generation of inflammatory mediators, and reverses the survival effect produced by inflammatory cytokines. Therefore, endogenous TauCl may help to suppress excessive inflammatory response in eosinophils at inflammatory sites.
authors.affiliation: Departamento de Farmacologia, Facultad de Medicina, Universidad de Valencia, Valencia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Martinez-Losa
authors.forename: J
authors.initials: J
authors.lastname: Cortijo
authors.forename: L
authors.initials: L
authors.lastname: Piqueras
authors.forename: M J
authors.initials: MJ
authors.lastname: Sanz
authors.forename: E J
authors.initials: EJ
authors.lastname: Morcillo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D047150:Eosinophil Cationic Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology; D017997:Leukotriene C4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000502:physiology; D016897:Respiratory Burst / Q000187:drug effects*; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D015848:Interleukin-5; D016328:NF-kappa B; D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K; D013481:Superoxides; D013654:Taurine; D017997:Leukotriene C4; C043410:N-chlorotaurine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009195:Peroxidase; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D047150:Eosinophil Cationic Protein; D002118:Calcium