Cardiotrophin-1 alters airway smooth muscle structure and mechanical properties in airway explants.
Induction of hypertrophy and inhibition of apoptosis may be important mechanisms contributing to increased airway smooth muscle (ASM) mass in asthma. Data from our laboratory indicate that cardiotrophin-1 (CT-1) induces hypertrophy and inhibits apoptosis in isolated human ASM cells. To determine whether these novel effects of CT-1 also occur in the airway tissue milieu and to determine whether structural changes are accompanied by functional changes, matched pairs of guinea pig airway explants were treated with or without CT-1 for 7 days, and structural features as well as isometric and isotonic contractile and relaxant mechanical properties were measured. CT-1 (0.2-5 ng/ml) increased both myocyte mass and extracellular matrix in a concentration-dependent fashion. CT-1 (10 ng/ml)-treated tissues exhibited a significant increase in passive tension at all lengths on day 7; at optimal length, passive tension generated by CT-1-treated tissues was 1.72 +/- 0.12 vs. 1.0 +/- 0.1 g for control. Maximal isometric stress was decreased in the CT-1-treated group on day 7 (0.39 +/- 0.10 kg/cm(2)) vs. control (0.77 +/- 0.15 kg/cm(2), P < 0.05). Isoproterenol-induced relaxant potency was reduced in CT-1-treated tissues, log EC(50) being -7.28 +/- 0.34 vs. -8.12 +/- 0.25 M in control, P < 0.05. These data indicate that CT-1 alters ASM structural and mechanical properties in the tissue environment and suggest that structural changes found in the airway wall in asthma are not necessarily associated with increased responsiveness.
The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, St. Paul's Hospital, 1081 Burrard St., Vancouver, B. C., Canada V6Z 1Y6.
Xueyan
X
Zheng
Danyi
D
Zhou
Chun Y
CY
Seow
Tony R
TR
Bai
D000818:Animals; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D016207:Cytokines; C092073:cardiotrophin 1; D007545:Isoproterenol