Role of MUC5AC in the pathogenesis of exercise-induced bronchoconstriction.
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.
Hallstrand
Teal S
TS
Department of Medicine, University of Washington, Seattle WA 98195-6522, USA. tealh@u.washington.edu
Debley
Jason S
JS
Farin
Federico M
FM
Henderson
William R
WR
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
D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D013373:Substance P; D015288:Neurokinin A