Proliferation is not increased in airway myofibroblasts isolated from asthmatics.
Airway mesenchymal cells, such as myofibroblasts and airway smooth muscle cells, contribute to inflammation, airway remodelling and hyperresponsiveness in asthma by excessive proliferation and inflammatory mediator production. Using endobronchial biopsies obtained from both nonasthmatic and asthmatic subjects, in situ proliferation was assessed by immunostaining for cyclin D1. The number of immunoreactive cells increased with asthma severity and was restricted to the epithelium and subepithelial connective tissue. Despite increases in smooth muscle area, cyclin D1 was not detected in cells in intact muscle bundles. Biopsy-derived cell cultures were characterised as predominantly myofibroblasts, and were assessed to determine whether proliferation and cytokine production varied with asthma status. Cell enumeration showed that basal proliferation was similar in cells from nonasthmatics and asthmatics, and mitogenic responses to fibroblast growth factor-2, thrombin or serum were either reduced or unchanged in cells from asthmatics. Interleukin (IL)-1-dependent granulocyte-macrophage colony-stimulating factor and IL-8 release was increased in cell supernatants from asthmatics. Thus, increased rates of cellular proliferation identified in situ in the asthmatic airway occurred outside the expanded smooth muscle compartment. Although reduced proliferative responses were observed in cultured myofibroblasts from asthmatics, the increased cytokine production by these cells suggests that this contributes to and may perpetuate ongoing inflammation in asthma.
Ward
J E
JE
Dept of Pharmacology, University of Melbourne, Melbourne, Victoria 3010, Australia.
Harris
T
T
Bamford
T
T
Mast
A
A
Pain
M C F
MC
Robertson
C
C
Smallwood
D
D
Tran
T
T
Wilson
J
J
Stewart
A G
AG
D000328:Adult; D000420:Albuterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology*; D001249:Asthma / Q000378:metabolism*; D001993:Bronchodilator Agents / Q000494:pharmacology; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D000068298:Fluticasone; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D000068299:Salmeterol Xinafoate; D014132:Trachea / Q000378:metabolism*
D000730:Androstadienes; D001993:Bronchodilator Agents; D019938:Cyclin D1; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol