Studies on the Mechanism of Mucin Secretion by Cells of the Porcine Tracheal Epithelium

Abstract

The effects of selected pharmacological agents on mucin secretion by the tracheal epithelium of piglets were studied using organ culture. Mucin release into the culture medium was reduced, and mucin retention by secretory cells of the mucosa and submucosal glands was increased, by colchicine, vinblastine sulfate, and cytochalasin B. Dibutyryl cyclic AMP had no significant effect. Although these agents have diverse and poorly understood influences on cell functions, the results suggest a possible role for microtubules and microfilaments in the intracellular movement and release of mucin. 96

Cellular and Molecular Biology of Airway Mucins

“…While it was clear that what we now refer to a mucociliary clearance through the combined effects of mucus secretion and ciliary beating were of paramount importance for the self-cleansing property of the airways, it was also recognized that the factors, which normally control this mechanism, were largely unknown (Randell and Boucher, 2006). During the first half of the 1980s, improved in vitro airway cell culture techniques, and advancements in detection and quantification of glycoproteins in mucus, were developed and applied to study the regulation of mucus secretion (Adler et al, 1981; Cheng et al, 1981; Wu and Smith, 1982; Adler et al, 1987; Whitcutt et al, 1988). Beginning in 1985, our laboratory began a systematic investigation of the cellular and molecular properties of the major glycoprotein component of airway mucus, the mucins.…”

Porcine Tracheal Goblet Cell Ultrastructure: A Three-Dimensional Reconstruction

“…Porcine trachea was used because it is quite similar morphologically and histochemically to that of humans. A large number of goblet cells containing granules of acidic mucin, as demonstrated by staining with aician blue at p H 2.5, populate the mucosa, and submucosal areas are replete with glands [12]. The three-dimentional reconstruction demonstrated several specific anatomic relationships between Golgi apparatus, secretory granules, MT, MF, and mitochondria that would be less evident if the study were limited to examination of single planes of section.…”

Production of Airway Secretions

“…Granule movement probably involves intracellular contractile elements, since agents such as colchicine and cytocalasin B (which block microtubules and microfilaments) increase glycoprotein retention by airway secretory cells. 5 Stimulus-secretion coupling in airway secretory cells requires an increase in intracellular free calcium (Ca 2+ ), which probably results both from Ca 2+ influx and from intracellular Ca 2+ mobilization, at a critical intracellular site. 6 This increase in free Ca 2+ activates energy-dependent (ATP-requiring) processes, leading to fusion of granule and cell membranes, and to release of granule contents.…”