Phospholipase C-activating Plasma Membrane Receptors and Calcium Signaling in Immortalized Human Airway Epithelial Cells

Abstract

Mechanical clearance of inhaled dust particles and microorganisms is an important part of the innate defense mechanisms of mammalian airways. Airway epithelia are composed of various cell types with different degrees of cell polarity. Serous cells regulate composition and volume of luminal periciliary fluid and mucus. Autocrine, paracrine, or neuronal messengers determine the secretory and reabsorptive rates of electrolytes and water via cAMP-or inositol triphosphate/calcium-mediated intracellular signals. Comparison of the expression of calcium-mobilizing receptor types (G protein-coupled-, growth factor-, and cytokine receptors) in two types of human immortalized airway epithelial cells (S9, 16HBE14o-) revealed that receptor populations were qualitatively and quantitatively different in the two cell types. Sustained calcium signals were elicited by activation of purinergic receptors in 16HBE14o-cells or muscarinic acetylcholine or histamine receptors in S9 cells. These G protein-coupled receptors mobilized calcium from intracellular stores and activated capacitative calcium influx. The experimental cells may represent different types of original airway epithelial cells and seem to be suited as model cells to study cell signaling and protein expression during interaction with pathogens or their secretory products (e.g., virulence factors).

Staphylococcus aureus Alpha-Toxin Mediates General and Cell Type-Specific Changes in Metabolite Concentrations of Immortalized Human Airway Epithelial Cells

“…The 16HBE14o − cells are highly polarized and all known characteristics indicate that these cells represent one type of serous cells at the surface of airway epithelia, whereas the less polarized S9 cells may represent an airway cell type that is derived from the lower layer of the bronchial epithelium [20], [23], [29].…”

“…S9 cells were originally derived from a cystic fibrosis patient, subsequently corrected by introduction of the gene encoding wild-type cystic fibrosis transmembrane conductance regulator (CFTR) through adenoviral transfer. 16HBE14o − cells were derived from the bronchial epithelium of a transplant patient, express wild-type CFTR and are commonly used for analysis of a polarized cell layer [20], [23].…”

S. aureushaemolysin A-induced IL-8 and IL-6 release from human airway epithelial cells is mediated by activation of p38- and Erk-MAP kinases and additional, cell type-specific signalling mechanisms

“…One cancer cell line (A549) of alveolar origin was used for comparison. 16HBE14o-cells were derived from normal bronchial epithelium, form high resistance epithelia-like cell monolayers with tight junctions and apical surface specializations and show responses to a variety of external stimuli that are very similar to those obtained in freshly isolated primary bronchial epithelial cells (Cozens et al, 1994;Gruenert et al, 2004;Eichstaedt et al, 2008). S9 cells were derived from a cystic fibrosis patient and had been corrected by introduction of the gene encoding wild-type cystic fibrosis transmembrane conductance regulator (CFTR) (Zeitlin et al, 1991;Flotte et al, 1993).…”

“…S9 cells were derived from a cystic fibrosis patient and had been corrected by introduction of the gene encoding wild-type cystic fibrosis transmembrane conductance regulator (CFTR) (Zeitlin et al, 1991;Flotte et al, 1993). They show many characteristics of bronchial cells involved in salt and water secretion (Eichstaedt et al, 2008). A549 cells are lung cancer cells derived from surfactant secreting type II pneumocytes (Lieber et al, 1976).…”

Virulence factors ofStaphylococcus aureusinduce Erk-MAP kinase activation and c-Fos expression in S9 and 16HBE14o- human airway epithelial cells

“…We used the immortalized human bronchial cell lines S9 and 16HBE14o-as model systems to study signaling effects of bacterial toxins because these cells may represent different types of airway epithelial cells and appear to have maintained many of the structural and functional characteristics of the original airway epithelial cells (10,12,15,22,56). The experiments revealed that some effects of bacterial factors on airway epithelial cell signaling were common to both types of cells while others were different, indicating that interaction of bacterial factors with host cells may be highly cell type specific.…”