title: Chemokine CC-ligand 5 production and eosinophil activation into the upper airways of aspirin-sensitive patients.
abstract: BACKGROUND
  Airway eosinophilia is a hallmark of aspirin-sensitive asthma/rhinitis.
  
  
  OBJECTIVE
  We have investigated chemokine CC-ligand 5 (CCL5) production and its association with eosinophil activation in the upper airways of aspirin-sensitive patients both in vivo and in vitro.
  
  
  METHODS
  Twenty aspirin-sensitive asthma/rhinosinusitis patients, 18 atopic-tolerant asthma/rhinosinusitis patients and 15 healthy control subjects took part in the study. All subjects were challenged with saline and lysine-acetylsalicylic acid (L-asa) on separate occasions. Nasal lavages were obtained at baseline and 120 min after challenge and analysed for mediators' release.
  
  
  RESULTS
  When compared with control subjects, the baseline levels of CCL5 were significantly increased in both sensitive and tolerant patients (there was no significant difference in CCL5 concentrations between these two groups, P>0.05). However, L-asa nasal challenge induced significantly increased levels of CCL5 in the sensitive patients but not in the tolerant subjects (median: 380 vs. 140 pg/mL, P<0.0001). Similarly, the concentrations of both eosinophil cationic protein (ECP) and cysteinil leukotriene (cys-LTs) were increased significantly in the aspirin-sensitive but not in the tolerant patients. There was a trend towards a significant correlation between CCL5 and ECP concentrations in the sensitive patients following L-ASA challenge. On incubation with aspirin, nasal tissue derived from aspirin-sensitive but not that derived from tolerant subjects released increased CCL5 levels in culture. As determined by immunohistochemistry, CCL5 was predominantly localized to the nasal airway epithelium.
  
  
  CONCLUSIONS
  Altogether, these findings suggest that CCL5 is released in aspirin-sensitive asthma/rhinosinusitis.
authors.affiliation: Department of Immunogenetics and Allergy, Instituto Nacional de Enfermedades Respiratorias, Calzada Tlalpan, México.
authors.forename: A
authors.initials: A
authors.lastname: Fuentes-Beltrán
authors.forename: R
authors.initials: R
authors.lastname: Montes-Vizuet
authors.forename: E
authors.initials: E
authors.lastname: Valencia-Maqueda
authors.forename: M C
authors.initials: MC
authors.lastname: Negrete-García
authors.forename: M de L
authors.initials: Mde L
authors.lastname: García-Cruz
authors.forename: L M
authors.initials: LM
authors.lastname: Teran
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000276:immunology*; D001241:Aspirin / Q000009:adverse effects / Q000276:immunology*; D001249:Asthma / Q000276:immunology*; D018946:Chemokine CCL5 / Q000032:analysis / Q000096:biosynthesis*; D004342:Drug Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D047150:Eosinophil Cationic Protein / Q000032:analysis / Q000276:immunology; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D015289:Leukotrienes / Q000032:analysis / Q000276:immunology; D008875:Middle Aged; D017817:Nasal Lavage Fluid / Q000737:chemistry / Q000276:immunology; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C483024:CCL5 protein, human; D018946:Chemokine CCL5; D015289:Leukotrienes; D047150:Eosinophil Cationic Protein; C479220:RNASE3 protein, human; D001241:Aspirin