Hypersecretion of mucin in response to inflammatory mediators by guinea pig tracheal epithelial cells in vitro is blocked by inhibition of nitric oxide synthase (original) (raw)

Airway Mucus: From Production to Secretion

2000

Mucus,hypersecretion,is a phenotype,associated,with multiple obstructive lung diseases. However, in spite of its nefarious reputation under pathological conditions, there are significant benefits to having low levels of mucus present in the airways at baseline, such as the ability to trap and,eliminate inhaled particles and to prevent,desiccation of airway,surfaces. Mucins are high molecular weight glycoproteins that are the chief components,that render,viscoelastic

Mucus hypersecretion in asthma: causes and effects

Current opinion in pulmonary medicine, 2009

Purpose of review-Airway mucus plugging has long been recognized as a principal cause of death in asthma. However, molecular mechanisms of mucin overproduction and secretion have not been understood until recently. These mechanisms are reviewed together with ongoing investigations relating them to lung pathophysiology.

Regulation of mucin secretion in the ferret trachea

Otolaryngology - Head and Neck Surgery, 1997

Mucin is the major component of mucus and can be used as a marker for mucus secretion. The purpose of this study was to develop an in vitro method to evaluate the regulation of mucin secretion. To do this, we used a sandwiched enzyme-linked lectin assay to measure mucin secretion from isolated ferret tracheal segments. This assay entailed coating microtiter plate wells with dolichos biflorus agglutinin and detecting the bound mucin that was secreted into a buffer solution by the tracheal segments. We used this method to evaluate the secretory response to four secretagogues: prostaglandin F2~ (PGF2~), adenosine triphosphate (ATP), methacholine, and human neutrophil elastase (HNE). Each agent stimulated mucin secretion above baseline secretion (ATP [p = 0.022], PGF2= [p = 0.009], and HNE [p < 0.05]), and the relative potency of these secretagogues was PGF2= _< ATP < MCh < HNE. We also demonstrated that there is an anatomic gradient for both constitutive and stimulated mucin secretion, with the distal tracheal segments secreting more mucin per gram of weight than the proximal segments. This fairly simple and reproducible technique can be used to evaluate the regulation of mucin secretion in the airway and to assess the efficacy of agents that might alter the secretory response. (Otolaryngol Head Neck Surg 1997; 117:480-6,) MUCUS hypersecretion is one of the major characteristics of chronic obstructive airway diseases including chronic bronchitis, cystic fibrosis, and sinusitis. Mucus is a complex mixture of mucins, ions, proteins, lipids, and water. Mucins are the major solid component of normal mucus, and these high molecular-weight glycoconjugates can be used as a marker for mucus secretion. Mucin secretion has been measured according to radioactive labeling 1 or an enzyme-linked immunosorbent assay (ELISA). 2 Radioactive macromolecules are usually recovered from culture fluid by precipitation or dialysis. However, the radioactive precursors are incorporated into not only mucin but also other macromole

Airway Mucus

American Journal of Respiratory Cell and Molecular Biology, 2006

Mucus hypersecretion is a phenotype associated with multiple obstructive lung diseases. However, in spite of its nefarious reputation under pathologic conditions, there are significant benefits to having low levels of mucus present in the airways at baseline, such as the ability to trap and eliminate inhaled particles and to prevent desiccation of airway surfaces. Mucins are high-molecular-weight glycoproteins that are the chief components that render viscoelastic and gel-forming properties to mucus. Recent advances in animal models and in vitro systems have provided a wealth of information regarding the identification of the mucin genes that are expressed in the lungs, the signal transduction pathways that regulate the expression of these mucins, and the secretory pathways that mediate their release into the airways. In addition, the clinical and pathologic literature has corroborated many of the basic laboratory findings. As a result, mucin overproduction and hypersecretion are moving away from being markers of disease and toward being testable as functional components of lung disease processes.

Mucin Is Produced by Clara Cells in the Proximal Airways of Antigen-Challenged Mice

American Journal of Respiratory Cell and Molecular Biology, 2004

Airway mucus hypersecretion is a prominent feature of many obstructive lung diseases. We thus determined the ontogeny and exocytic phenotype of mouse airway mucous cells. In naive mice, ciliated ‫ف(‬ 40%) and nonciliated ‫ف(‬ 60%) epithelial cells line the airways, and Ͼ 95% of the nonciliated cells are Clara cells that contain Clara cell secretory protein (CCSP). Mucous cells comprise Ͻ 5% of the nonciliated cells. After sensitization and a single aerosol antigen challenge, alcian blue-periodic acid Schiff's positive mucous cell numbers increase dramatically, appearing 6 h after challenge (21% of nonciliated/nonbasal cells), peaking from Days 1-7 (99%), and persisting at Day 28 (65%). Throughout the induction and resolution of mucous metaplasia, ciliated and Clara cell numbers identified immunohistochemically change only slightly. Intracellular mucin content peaks at Day 7, and mucin expression is limited specifically to a Clara cell subset in airway generations 2-4 that continue to express CCSP. Functionally, Clara cells are secretory cells that express the regulated exocytic marker Rab3D and, in antigen-challenged mice, rapidly secrete mucin in response to inhaled ATP in a dose-dependent manner. Thus, Clara cells show great plasticity in structure and secretory products, yet have molecular and functional continuity in their identity as specialized apical secretory cells. Mucus hypersecretion is a prominent feature of obstructive lung pathologies that, despite long recognition of its contributions to disease morbidities, is not yet sufficiently understood to treat directly. In cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and fatal asthma, mucus plugs occlude small airways (1-4). In CF and COPD, excess mucus in the airways contributes to disease morbidity by increasing the frequency and severity of pulmonary infections (5, 6) and the severity of airflow obstruction (7, 8). The airways of healthy individuals contain few mucous cells, but the airways of humans with asthma and of animals in induced models of asthma display dramatically increased numbers of mucin-producing goblet cells. This trait is commonly referred to as mucous (or goblet) cell metaplasia based on histopathologic criteria. While many of the immuno-(

Mucus Hypersecretion in Chronic Obstructive Pulmonary Disease and Its Treatment

Mediators of Inflammation

Most patients diagnosed with chronic obstructive pulmonary disease (COPD) present with hallmark features of airway mucus hypersecretion, including cough and expectoration. Airway mucus function as a native immune system of the lung that severs to trap particulate matter and pathogens and allows them to clear from the lung via cough and ciliary transport. Chronic mucus hypersecretion (CMH) is the main factor contributing to the increased risk of morbidity and mortality in specific subsets of COPD patients. It is, therefore, primarily important to develop medications that suppress mucus hypersecretions in these patients. Although there have been some advances in COPD treatment, more work remains to be done to better understand the mechanism underlying airway mucus hypersecretion and seek more effective treatments. This review article discusses the structure and significance of mucus in the lungs focusing on gel-forming mucins and the impacts of CMH in the lungs. Furthermore, we summar...