title: Role of MUC5AC in the pathogenesis of exercise-induced bronchoconstriction.
abstract: BACKGROUND
  The pathogenesis of exercise-induced bronchoconstriction (EIB) involves the release of mediators from several airway cells in response to exercise challenge, but the mechanism leading to airflow obstruction during EIB is incompletely understood.
  
  
  OBJECTIVE
  To evaluate the role of secreted mucin in the pathogenesis of EIB.
  
  
  METHODS
  Induced sputum was collected at baseline and 30 minutes after exercise challenge in patients with asthma with EIB. The expression of gel-forming mucins and epidermal growth factor receptor ligands were assessed by quantitative polymerase chain reaction. Secreted mucin 5AC (MUC5AC), the eicosanoids cysteinyl leukotrienes (cysLTs) and 15S-hydroxyeicosatetraenoic acid (15S-HETE), and tachykinins neurokinin A (NKA) and substance P (SP) were measured in induced sputum supernatant.
  
  
  RESULTS
  Among the gel-forming mucins, MUC5AC was expressed at the highest level. The gene expression of MUC5AC increased after exercise challenge compared with baseline and was associated with EIB severity by regression analysis. The relative levels of MUC5AC in induced sputum increased from a geometric mean of 9.5 at baseline to 18.4 postexercise challenge. Associations between the levels of MUC5AC and cysLTs and between the levels of cysLTs and NKA postexercise challenge were identified by regression analysis.
  
  
  CONCLUSIONS
  These data indicate that (1) the predominant gel-forming mucin expressed in induced sputum of patients with asthma with EIB is MUC5AC; (2) an increase in MUC5AC gene expression and release of MUC5AC protein occurs after exercise challenge; and (3) MUC5AC release may occur through the cysLT-associated activation of sensory airway nerves.
authors.affiliation: Department of Medicine, University of Washington, Seattle WA 98195-6522, USA. tealh@u.washington.edu
authors.forename: Teal S
authors.initials: TS
authors.lastname: Hallstrand
authors.forename: Jason S
authors.initials: JS
authors.lastname: Debley
authors.forename: Federico M
authors.initials: FM
authors.lastname: Farin
authors.forename: William R
authors.initials: WR
authors.lastname: Henderson
mesh_terms: D000293:Adolescent; D000328:Adult; D001250:Asthma, Exercise-Induced / Q000378:metabolism*; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC; D009077:Mucins / Q000378:metabolism*; D015288:Neurokinin A / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013183:Sputum / Q000737:chemistry; D013373:Substance P / Q000378:metabolism
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D013373:Substance P; D015288:Neurokinin A