Expression of c-erbB receptors and ligands in the bronchial epithelium of asthmatic subjects

Background: The c-erbB family of receptor tyrosine kinases act in a combinatorial fashion to regulate cell behavior. Disturbances in this system have been associated with neoplastic and inflammatory diseases. Objectives: Although expression of the epidermal growth factor receptor (EGFR; c-erbB1) is...

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Published in:	Journal of allergy and clinical immunology Vol. 109; no. 1; pp. 75 - 81
Main Authors:	Polosa, Riccardo, Puddicombe, Sarah M., Krishna, M.Thirumala, Tuck, Angela B., Howarth, Peter H., Holgate, Stephen T., Davies, Donna E.
Format:	Journal Article
Language:	English
Published:	New York, NY Mosby, Inc 01-01-2002 Elsevier Elsevier Limited
Subjects:	Adult Allergic diseases Asthma Asthma - metabolism Biological and medical sciences Bronchi - chemistry bronchial epithelium c-ErbB protein Cloning Cystic fibrosis Epidermal growth factor Epidermal Growth Factor - analysis Epithelium - chemistry erbB receptor ErbB Receptors - analysis Female Heparin-binding EGF-like Growth Factor Humans Immunohistochemistry Immunopathology Intercellular Signaling Peptides and Proteins Ligands Male Medical sciences phosphorylation Polyclonal antibodies Receptor, ErbB-2 - analysis Receptor, ErbB-3 - analysis Respiratory and ent allergic diseases Studies Transforming Growth Factor alpha - analysis transforming growth factor α wound repair wound repair EGF HB-EGF erbB receptor EGFR Asthma HER TGF-α transforming growth factor α SFM epidermal growth factor bronchial epithelium phosphorylation Human Immunohistochemistry Immunopathology Allergy Phosphorylation Respiratory disease Enzyme Pathogenesis Transferases Epidermal growth factor Transforming growth factor α Obstructive pulmonary disease Protein-tyrosine kinase Biological receptor
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Summary:	Background: The c-erbB family of receptor tyrosine kinases act in a combinatorial fashion to regulate cell behavior. Disturbances in this system have been associated with neoplastic and inflammatory diseases. Objectives: Although expression of the epidermal growth factor receptor (EGFR; c-erbB1) is increased in the bronchial epithelium in asthma, there is no information on expression of other members of the c-erbB receptor and ligand family that can modulate EGFR function. Methods: Immunohistochemistry was used to compare expression of EGFR, c-erbB2, c-erbB3, epidermal growth factor, heparin-binding epidermal growth factor–like growth factor, and transforming growth factor α in bronchial biopsy specimens from normal and asthmatic subjects. Scrape-wounded monolayers of 16HBE 14o– cells were used as an in vitro model of damage and repair. Changes in EGFR, c-erbB2, and c-erbB3 distribution were measured by means of immunocytochemistry, whereas tyrosine phosphorylation was measured by means of immunoprecipitation and Western blotting. Results: Although epithelial staining for the EGFR was significantly increased in asthmatic epithelium (P < .001), there was no difference in staining for the other receptors and ligands studied. In scrape-wounded epithelial monolayers, tyrosine phosphorylation of EGFR, c-erbB2, and c-erbB3 occurred immediately after damage; however, only EGFR showed a change in expression in response to damage. Conclusions: Even though EGFR levels are increased in asthma, this is not linked to changes in expression of its activating ligands or other c-erbB receptors. Because bronchial epithelial cells respond to physical damage through activation of several c-erbB family members, the shift in favor of increased EGFR levels in asthma may lead to altered epithelial function by influencing the number and type of heterodimeric signaling complexes, assuming sufficient ligand availability. (J Allergy Clin Immunol 2002;109:75-81.)
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0091-6749 1097-6825
DOI:	10.1067/mai.2002.120274