title: Inhibitory effects of N-acetylcysteine on the functional responses of human eosinophils in vitro.
abstract: BACKGROUND
  Oxidative stress appears to be relevant in the pathogenesis of inflammation in allergic diseases like bronchial asthma. Eosinophils are oxidant-sensitive cells considered as key effectors in allergic inflammation.
  
  
  OBJECTIVE
  The aim of this work was to study the effects of the clinically used antioxidant N-acetyl-L-cysteine (NAC) on the functional responses of human-isolated eosinophils.
  
  
  METHODS
  Human eosinophils were purified from the blood of healthy donors by a magnetic bead separation system. The effects of NAC were investigated on the generation of reactive oxygen species (chemiluminescence and flow cytometry), Ca(2+) signal (fluorimetry), intracellular glutathione (GSH; flow cytometry), p47(phox)-p67(phox) translocation (Western blot) and eosinophil cationic protein (ECP) release (radioimmunoassay).
  
  
  RESULTS
  NAC (0.1-1 mm) inhibited the extracellular generation of oxygen species induced by N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) and eotaxin (in the presence of IL-5) with -logIC(50) values of 3.61+/-0.03 and 3.36+/-0.09, respectively. Also, the intracellular generation of hydrogen peroxide was virtually abolished by NAC (0.5-1 mm). NAC (1 mm) did not alter the fMLP-induced Ca(2+) signal but augmented the eosinophil content of reduced GSH and inhibited p47(phox)-p67(phox) translocation. NAC inhibited the release of ECP ( approximately 90% inhibition at 1 mm) from fMLP-activated eosinophils.
  
  
  CONCLUSIONS
  Inhibition by NAC of human eosinophil functions in vitro is potentially useful in the treatment of allergic inflammation.
authors: Department of Pharmacology, University of Valencia, Valencia, Spain.
authors: M
authors: M
authors: Martinez-Losa
authors: J
authors: J
authors: Cortijo
authors: G
authors: G
authors: Juan
authors: J E
authors: JE
authors: O'Connor
authors: M J
authors: MJ
authors: Sanz
authors: F
authors: F
authors: Santangelo
authors: E J
authors: EJ
authors: Morcillo
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D016923:Cell Death / Q000187:drug effects; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000037:antagonists & inhibitors / Q000494:pharmacology; D047150:Eosinophil Cationic Protein / Q000097:blood; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000097:blood; D006801:Humans; D049449:Luminescence; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019255:NADPH Oxidases / Q000097:blood; D010750:Phosphoproteins / Q000097:blood; D017382:Reactive Oxygen Species / Q000378:metabolism; D014178:Translocation, Genetic / Q000187:drug effects
chemical_list: C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016166:Free Radical Scavengers; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; C079789:neutrophil cytosol factor 67K; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D047150:Eosinophil Cationic Protein; C479220:RNASE3 protein, human; D005978:Glutathione; D002118:Calcium; D000111:Acetylcysteine