Differentiation of Human Airway Epithelia is Dependent on Erbb2.
From: Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, 52242, USA.
American journal of physiology. Lung cellular and molecular physiology
- Publish Date: Aug 2006
- ISSN: 1040-0605
- Volume: 291
- Issue: 2
- Pages: L175-80
- Medium: Print
- Language: English
- Citation (JAMA): Vermeer Paola D, Panko Lacey, Karp Philip, et al. Differentiation of Human Airway Epithelia is Dependent on Erbb2.. Am. J. Physiol. Lung Cell Mol. Physiol. Aug 2006;291:L175-80
Abstract
A clinical case documented a reversible change in airway epithelial differentiation that coincided with the initiation and discontinuation of trastuzumab, an anti-erbB2 antibody. This prompted the investigation into whether blocking the erbB2 receptor alters differentiation of the airway epithelium. To test this hypothesis, we treated an in vitro model of well-differentiated human airway epithelia with trastuzumab or heregulin-alpha, an erbB ligand. In addition, coculturing with human lung fibroblasts tested whether in vivo subepithelial fibroblasts function as an endogenous source of ligands able to activate erbB receptors expressed by the overlying epithelial cells. Epithelia were stained with hematoxylin and eosin and used for morphometric analysis. Trastuzumab treatment decreased the ciliated cell number by 49% and increased the metaplastic, flat cell number by 640%. Heregulin-alpha treatment increased epithelial height and decreased the number of metaplastic and nonciliated columnar cells, whereas it increased the goblet cell number. We found that normal human lung fibroblasts express transforming growth factor-alpha, heparin-binding epidermal-like growth factor, epiregulin, heregulin-alpha, and amphiregulin, all of which are erbB ligands. Cocultures of airway epithelia with primary fibroblasts increased epithelial height comparable to that achieved following heregulin-alpha treatment. These data show that erbB2 stimulation is required for maintaining epithelial differentiation. Furthermore, the mesenchyme underlying the airway epithelium secretes a variety of erbB ligands that may direct various pathways of epithelial differentiation.
Mesh Headings (Keywords): Antibodies, Monoclonal, Antineoplastic Agents, Cell Differentiation, Cells, Cultured, Coculture Techniques, Epithelial Cells, Female, Fibroblasts, Humans, Middle Aged, Neuregulin-1, Receptor, erbB-2, Respiratory Mucosa
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