Am. J. Respir. Crit. Care Med., Volume 165, Number 2, January 2002, 266-272

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

ANNETTE T. HASTIE, WALTER K. KRAFT, KRISTIN B. NYCE, JAMES G. ZANGRILLI, ALI I. MUSANI, JAMES E. FISH, and STEPHEN P. PETERS

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

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 × 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 × 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.

This article has been cited by other articles:

				D. M. Murphy, I. A. Forrest, P. A. Corris, G. E. Johnson, T. Small, D. Jones, A. J. Fisher, J. J. Egan, T. E. Cawston, C. Ward, et al. Simvastatin attenuates release of neutrophilic and remodeling factors from primary bronchial epithelial cells derived from stable lung transplant recipients Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L592 - L599. [Abstract] [Full Text] [PDF]

				A. Semlali, E. Jacques, S. Plante, S. Biardel, J. Milot, M. Laviolette, L.-P. Boulet, and J. Chakir TGF- Suppresses EGF-Induced MAPK Signaling and Proliferation in Asthmatic Epithelial Cells Am. J. Respir. Cell Mol. Biol., February 1, 2008; 38(2): 202 - 208. [Abstract] [Full Text] [PDF]

				H. Sugiura, X. Liu, F. Duan, S. Kawasaki, S. Togo, K. Kamio, X. Q. Wang, L. Mao, Y. Ahn, R. F. Ertl, et al. Cultured Lung Fibroblasts from Ovalbumin-Challenged "Asthmatic" Mice Differ Functionally from Normal Am. J. Respir. Cell Mol. Biol., October 1, 2007; 37(4): 424 - 430. [Abstract] [Full Text] [PDF]

				M. M. Choe, P. H. S. Sporn, and M. A. Swartz Extracellular Matrix Remodeling by Dynamic Strain in a Three-Dimensional Tissue-Engineered Human Airway Wall Model Am. J. Respir. Cell Mol. Biol., September 1, 2006; 35(3): 306 - 313. [Abstract] [Full Text] [PDF]

				W. W. Busse, A. Wanner, K. Adams, H. Y. Reynolds, M. Castro, B. Chowdhury, M. Kraft, R. J. Levine, S. P. Peters, and E. J. Sullivan Investigative Bronchoprovocation and Bronchoscopy in Airway Diseases Am. J. Respir. Crit. Care Med., October 1, 2005; 172(7): 807 - 816. [Abstract] [Full Text] [PDF]

				M. M. Kelly, R. Leigh, P. Bonniaud, R. Ellis, J. Wattie, M. J. Smith, G. Martin, M. Panju, M. D. Inman, and J. Gauldie Epithelial Expression of Profibrotic Mediators in a Model of Allergen-Induced Airway Remodeling Am. J. Respir. Cell Mol. Biol., February 1, 2005; 32(2): 99 - 107. [Abstract] [Full Text] [PDF]

				S. T. Holgate, J. Holloway, S. Wilson, F. Bucchieri, S. Puddicombe, and D. E. Davies Epithelial-Mesenchymal Communication in the Pathogenesis of Chronic Asthma Proceedings of the ATS, April 1, 2004; 1(2): 93 - 98. [Abstract] [Full Text] [PDF]

				N. M. Nikolaidis, N. Zimmermann, N. E. King, A. Mishra, S. M. Pope, F. D. Finkelman, and M. E. Rothenberg Trefoil Factor-2 Is an Allergen-Induced Gene Regulated by Th2 Cytokines and STAT6 in the Lung Am. J. Respir. Cell Mol. Biol., October 1, 2003; 29(4): 458 - 464. [Abstract] [Full Text] [PDF]

				J. Jagnow and S. Clegg Klebsiella pneumoniae MrkD-mediated biofilm formation on extracellular matrix- and collagen-coated surfaces Microbiology, September 1, 2003; 149(9): 2397 - 2405. [Abstract] [Full Text] [PDF]

				J. M. Madison Migration of Airway Smooth Muscle Cells Am. J. Respir. Cell Mol. Biol., July 1, 2003; 29(1): 8 - 11. [Full Text] [PDF]

				G. Pelaia, G. Cuda, A. Vatrella, D. Fratto, R. D. Grembiale, P. Tagliaferri, R. Maselli, F. S. Costanzo, and S. A. Marsico Effects of Transforming Growth Factor-{beta} and Budesonide on Mitogen-Activated Protein Kinase Activation and Apoptosis in Airway Epithelial Cells Am. J. Respir. Cell Mol. Biol., July 1, 2003; 29(1): 12 - 18. [Abstract] [Full Text] [PDF]

				M. J. Tobin Asthma, Airway Biology, and Nasal Disorders in AJRCCM 2002 Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 319 - 332. [Full Text] [PDF]