Differentiation of human airway epithelia is dependent on erbB2

Paola D Vermeer; Lacey Panko; Philip Karp; John H Lee; Joseph Zabner

doi:10.1152/ajplung.00547.2005

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Differentiation of human airway epithelia is dependent on erbB2

Journal article

Peer reviewed

Differentiation of human airway epithelia is dependent on erbB2

Paola D Vermeer, Lacey Panko, Philip Karp, John H Lee and Joseph Zabner

American journal of physiology. Lung cellular and molecular physiology, Vol.291(2), pp.L175-180

08/2006

DOI: 10.1152/ajplung.00547.2005

PMID: 16489114

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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.

Respiratory Mucosa - cytology

Respiratory Mucosa - drug effects

Fibroblasts - physiology

Antibodies, Monoclonal - pharmacology

Coculture Techniques

Epithelial Cells - drug effects

Humans

Middle Aged

Cells, Cultured

Receptor, ErbB-2 - metabolism

Neuregulin-1 - pharmacology

Antibodies, Monoclonal, Humanized

Epithelial Cells - physiology

Female

Antineoplastic Agents - pharmacology

Fibroblasts - cytology

Epithelial Cells - cytology

Cell Differentiation - physiology

Trastuzumab

Details

Title: Subtitle: Differentiation of human airway epithelia is dependent on erbB2
Creators: Paola D Vermeer - Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, 52242, USA
Lacey Panko
Philip Karp
John H Lee
Joseph Zabner
Resource Type: Journal article
Publication Details: American journal of physiology. Lung cellular and molecular physiology, Vol.291(2), pp.L175-180
DOI: 10.1152/ajplung.00547.2005
PMID: 16489114
ISSN: 1040-0605
eISSN: 1522-1504
Grant note: HL-61234 / NHLBI NIH HHS HL-075276-01A / NHLBI NIH HHS
Language: English
Date published: 08/2006
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
Record Identifier: 9984094212702771

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