FSS- acquisition of data; analysis and interpretation Erlotinib buy of data. LMMBP- conceived of the study, and participated in its design and coordination and helped to draft the manuscript. FJC-study supervision All authors read and approved the final manuscript. Acknowledgements The authors acknowledge the CAPES (Centro de Aperfei?oamento de Pessoal do Ensino Superior) that supported this study. The authors declare that they do not have anything to disclose regarding funding from industries or conflict of interest with respect to this manuscript.
in the conducting airways, the tracheobronchial glands are a major source of mucus, the heterogeneous secretion rich in mucins and containing various antimicrobial and immunological products that is vital to maintaining healthy lungs (15).
These branched tubuloacinar glands contain two primary secretory cell types: mucous and serous cells. Serous cells are generally found as an acinar demilune, whereas mucous cells line the secretory tubules leading from the acini to the airway surface (45). Like the surface goblet cells, the primary secretory products of mucous cells are mucins (50). By contrast, the predominant secretions of serous cells are believed to be various antimicrobial compounds (16). In addition to macromolecules, mucous glands secrete significant volumes of water, secondary to active secretion of Cl? and HCO3? (3, 64, 68). On the basis of their location it has generally been assumed that serous cells are responsible for the bulk of gland fluid production, a view supported by early immunocytochemical data showing the predominant location of CFTR in the lung is gland serous cells (14, 31, 49).
Although this result has not always been confirmed by others (38), recent studies have convincingly demonstrated CFTR in the apical membrane of serous cells by both immunocytochemistry and functional analysis (39�C41). Recent studies suggest that mucous cells also secrete fluid. Thus we have shown that gland cultures of mucous phenotype secrete as much Cl? as those of serous phenotype (20). Also suggestive of secretion of liquid by mucous cells secrete is the finding in intact glands that fluid flow along the gland lumen continues to increase at 50 ��m from the termination of the tubule, a point presumably some distance beyond the serous demilune (68). Here, we further characterize our human airway gland mucous cell model.
Metabolic labeling and biochemical analysis show that the cells synthesize and release mucin glycoprotein, and studies of mucin gene and glycoprotein expression demonstrate that they resemble their native counterparts. In CF, gland secretions are abnormally viscous and there is evidence from cell GSK-3 cultures that Cl? and liquid secretion are less than normal (33, 34, 69). Given the evidence discussed above that mucous cells may contribute to gland liquid secretions, we have also investigated the effects of CF on Cl? secretion by mucous gland cultures.