Epidermal growth factor-like molecular species in normal bronchoalveolar lavage fluid

Kumar, Rakesh; O'grady, Roslynn; Girolamo, Nick Di

doi:10.1007/bf00173309

Cited by 10 publications

(6 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we extended these observations by demonstrating glandular expression of TGF-␣, HB-EGF, AR, and BTC in human lung. It is likely that all of these growth factors contribute to the EGF-like growth factor activity that is secreted into the fluid that bathes the apical surface of the bronchial epithelium (53). In our study we also observed immunostaining for EGF, TGF-␣, HB-EGF and AR, but not BTC, between the basal and columnar epithelial cells.…”

Section: Discussionsupporting

confidence: 67%

Expression of c-erbB Receptors and Ligands in Human Bronchial Mucosa

Polosa

Prosperini

Leir

et al. 1999

Am J Respir Cell Mol Biol

113

View full text Add to dashboard Cite

The epidermal growth factor receptor (EGFR, c-erbB1) plays a pivotal role in maintenance and repair of epithelial tissues; however, little is known about coexpression of c-erbB receptors and their ligands in human bronchial epithelium. We therefore analyzed the expression of these molecules in cultured bronchial epithelial cells and normal bronchial mucosa, using reverse transcription-polymerase chain reaction (RT- PCR), flow cytometry, and immunohistochemistry. Messenger RNA (mRNA) encoding EGFR, c-erbB2, and c-erbB3, but not c-erbB4, was detected in primary cultures of human bronchial epithelial cells, as well as in the human bronchial epithelial-derived cell lines H292 and 16HBE 14o-. Transcripts encoding epidermal growth factor (EGF), heparin binding epidermal growth factor (HB-EGF), transforming growth factor-alpha (TGF-alpha), and amphiregulin (AR) were also detected, and expression of the three receptors and four ligands was confirmed by immunocytochemical staining of the cultured cells. Immunohistochemical analysis of resin- or paraffin-embedded sections from surgical specimens of bronchial mucosa revealed strong membrane staining for EGFR within the bronchial epithelium; this was particularly evident between basal cells and the basal aspect of columnar cells. The patterns of staining for c-erbB2 and c-erbB3 in the bronchial epithelium were similar to those for EGFR. Immunostaining for EGF, TGF-alpha, AR, HB- EGF, and betacellulin (BTC) was intense in the submucosal glands; with the exception of BTC, EGFR ligand immunoreactivity was also observed in the bronchial epithelium, where it paralleled EGFR staining. Colocalization of c-erbB receptors and ligands demonstrates the potential for productive c-erbB receptor interactions in bronchial epithelium. Further study of these interactions may help to define their role in maintenance and repair of the bronchial epithelium.

show abstract

Section: Discussionsupporting

confidence: 67%

Expression of c-erbB Receptors and Ligands in Human Bronchial Mucosa

Polosa

Prosperini

Leir

et al. 1999

Am J Respir Cell Mol Biol

113

View full text Add to dashboard Cite

show abstract

“…As EGFR levels increase in the skin [22], gastrointestinal tract [23] and lungs [24, 25] in response to tissue injury, the high levels observed throughout the epithelium of severe asthmatic subjects would suggest that there is widespread, ongoing stress and damage in the airways. In normal epithelium, EGFRs are expressed on the basolateral surface [1] and are spatially separate from their activating ligands contained in the apical lining fluid [26]. In contrast, in severe asthma EGFR immunostaining is also evident on the apical surface suggesting the potential for cognate ligand receptor interactions [1].…”

Section: Discussionmentioning

confidence: 99%

The role of the epidermal growth factor receptor in sustaining neutrophil inflammation in severe asthma

Hamilton

Torres-Lozano

Puddicombe

et al. 2003

Clin Experimental Allergy

134

115

View full text Add to dashboard Cite

show abstract

“…In these areas of epithelium, membrane staining for the EGFR was particularly intense and was evident on all surfaces including the apical surface (Fig. 1D, F), which is reported to be bathed in secretory fluid containing EGF-like growth factors (37). In contrast, epithelial immunostaining in areas of biopsy-induced damage from normal subjects was not affected (Fig.…”

Section: Analysis Of Egfr Expression In Bronchial Epithelium Of Mild mentioning

confidence: 91%

Involvement of the epidermal growth factor receptor in epithelial repair in asthma

Puddicombe¹

2000

The FASEB Journal

427

337

View full text Add to dashboard Cite

Epithelial damage and airway remodeling are consistent features of bronchial asthma and are correlated with disease chronicity, severity, and bronchial hyperreactivity. To examine the mechanisms that control bronchial epithelial repair, we investigated expression of the epidermal growth factor receptor (c-erbB1, EGFR) in asthmatic bronchial mucosa and studied repair responses in vitro. In biopsies from asthmatic subjects, areas of epithelial damage were frequently observed and exhibited strong EGFR immunostaining. EGFR expression was also high in morphologically intact asthmatic epithelium. Using image analysis, EGFR immunoreactivity (% of total epithelial area, median (range) was found to increase from 9.4 (4.1-20.4) in normal subjects (n=10) to 18.4 (9.3-28.9) in mild asthmatics (P<0.01, n=13) and 25.4 (15.4-31.8) in severe asthmatics (P<0.00, n=5). Epithelial EGFR immunoreactivity remained elevated in patients treated with corticosteroids and was positively correlated with subepithelial reticular membrane thickening. Using 16HBE 14o- bronchial epithelial cells, we found that EGF accelerated repair of scrape-wounded monolayers and that the EGFR-selective inhibitor, tyrphostin AG1478, inhibited both EGF-stimulated and basal wound closure whereas dexamethasone was without effect. Intrinsic activation of the EGFR was confirmed by analysis of tyrosine phosphorylated proteins, which revealed a rapid, damage-induced phosphorylation of the EGFR, irrespective of the presence of exogenous EGF. To assess the relationship between EGFR-mediated repair and tissue remodeling, release of the profibrogenic mediator TGF-beta2 was also measured. Scrape wounding increased release of TGF-beta2 from epithelial monolayers and EGF had no additional stimulatory effect. However, when repair was retarded with AG1478, the amount of TGF-beta2 increased significantly. These data indicate that the EGFR may play an important role in bronchial epithelial repair in asthma and that impairment of this function may augment airway remodeling.

show abstract

Epidermal growth factor-like molecular species in normal bronchoalveolar lavage fluid

Cited by 10 publications

References 28 publications

Expression of c-erbB Receptors and Ligands in Human Bronchial Mucosa

Expression of c-erbB Receptors and Ligands in Human Bronchial Mucosa

The role of the epidermal growth factor receptor in sustaining neutrophil inflammation in severe asthma

Involvement of the epidermal growth factor receptor in epithelial repair in asthma

Contact Info

Product

Resources

About