Asthmatic epithelial cell proliferation and stimulation of collagen production: human asthmatic epithelial cells stimulate collagen type III production by human lung myofibroblasts after segmental allergen challenge.
Epithelial injury and subepithelial collagen deposition are characteristic of asthma. We hypothesized that epithelial cell proliferation increases after airway injury in asthmatics, that epithelial cells stimulate lung myofibroblast collagen production, and that both processes are modulated by allergen-recruited inflammatory cells. Epithelial cells obtained at baseline, 1 d, and 1 and 2 wk after endobronchial allergen challenge from asthmatics and nonasthmatics were placed in culture, with and without bronchoalveolar lavage cells obtained from the same segment. Epithelial cell proliferation and collagen synthesis by human lung myofibroblasts stimulated with culture medium from these epithelial cells were determined. Epithelial proliferation increased (108 +/- 50% above baseline, p = 0.01 for d, and p = 0.004 for group x day interaction) 1 wk postchallenge in cells from asthmatics, but not from nonasthmatics, and required bronchoalveolar lavage cell coculture. Culture medium from epithelium harvested from asthmatics, but not from nonasthmatics, at 1 to 2 wk postchallenge stimulated collagen type III production 50% to 70% (p = 0.043 for clinical group, p = 0.012 for day, and p = 0.022 for group x day interaction), but not collagen type I. This effect was independent of an acute eosinophilic response. We conclude that epithelial cells from asthmatics, but not from nonasthmatics, are stimulated to proliferate after allergen challenge, and over 1 to 2 wk postchallenge, stimulate collagen type III synthesis by lung myofibroblasts. Epithelial cell proliferation appears dependent upon infiltrating inflammatory cells, but stimulation of collagen type III does not.
Hastie
Annette T
AT
Department of Medicine, Division of Critical Care, Pulmonary, Allergic & Immunologic Diseases, and Division of Clinical Pharmacology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
Kraft
Walter K
WK
Nyce
Kristin B
KB
Zangrilli
James G
JG
Musani
Ali I
AI
Fish
James E
JE
Peters
Stephen P
SP
D000328:Adult; D001249:Asthma / Q000378:metabolism*; D015153:Blotting, Western; D001985:Bronchial Provocation Tests; D018893:Bronchoalveolar Lavage; D001999:Bronchoscopy; D018929:Cell Culture Techniques; D024061:Collagen Type III / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D009210:Myofibrils / Q000378:metabolism*; D013997:Time Factors
D024061:Collagen Type III