Expression of ADAMs ("a disintegrin and metalloprotease") in the human lung
Antoon Dijkstra1, Dirkje S Postma, Jacobien A Noordhoek
1Department of Pulmonology, University Medical Center Groningen and University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Abstract:
In view of the associations of "a disintegrin and metalloprotease" (ADAM) with respiratory diseases, we assessed the expression of various ADAMs in human lung tissue. Lung tissue was obtained from nine individuals who underwent surgery for lung cancer or underwent lung transplantation for emphysema. Also, 16HBE 14o- (human bronchial epithelial) and A549 (alveolar type II epithelium-like) cell lines were used. Immunohistochemistry was performed with antibodies recognizing different ADAM domains. The ADAMs were typically distributed over the bronchial epithelium. ADAM8 and ADAM10 were expressed diffusely in all layers of the epithelium. ADAM9, ADAM17, and ADAM19 were predominantly expressed in the apical part of the epithelium, and ADAM33 was predominantly and strongly expressed in basal epithelial cells. In smooth muscle, ADAM19 and ADAM17 were strongly expressed, as was ADAM33, though this expression was weaker. ADAM33 was strongly expressed in vascular endothelium. All ADAMs were generally expressed in inflammatory cells. The typical distribution of ADAMs in the lung, especially in the epithelium, is interesting and suggests a localized function. As most ADAMs are involved in release of (pro-) inflammatory mediators and growth factors, they may play an important role in the first line of defense and in initiation of repair events in the airways.
Insights
This study maps the expression of ADAM proteins in human lung tissue and bronchial epithelial cells, revealing specific localizations that suggest roles in airway defense and repair.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Cell Biology
Background:
- A disintegrin and metalloprotease (ADAM) proteins are implicated in various respiratory diseases.
- Understanding ADAM expression in the lung is crucial for elucidating their role in respiratory health and disease.
Purpose of the Study:
- To investigate the expression patterns of various ADAM proteins in human lung tissue and cell lines.
- To determine the specific localization of ADAMs within different lung compartments, including epithelium, smooth muscle, and endothelium.
Main Methods:
- Human lung tissue from cancer surgery and transplantation patients was analyzed.
- Human bronchial epithelial (16HBE 14o-) and alveolar epithelial (A549) cell lines were utilized.
- Immunohistochemistry was performed using antibodies targeting different ADAM domains.
Main Results:
- ADAM proteins showed distinct distributions within the bronchial epithelium, with some expressed diffusely (ADAM8, ADAM10) and others localized apically (ADAM9, ADAM17, ADAM19) or basally (ADAM33).
- ADAM33 was notably expressed in basal epithelial cells and vascular endothelium.
- ADAM19, ADAM17, and ADAM33 were observed in smooth muscle, and all ADAMs were present in inflammatory cells.
Conclusions:
- The specific localization of ADAMs in the lung suggests specialized functions, particularly within the airway epithelium.
- ADAMs likely play a significant role in the lung's first line of defense and in initiating airway repair processes.
- These findings provide a foundation for further research into ADAMs' involvement in respiratory diseases.
