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Physiological Reviews Oct 2022The mucus clearance system is the dominant mechanical host defense system of the human lung. Mucus is cleared from the lung by cilia and airflow, including both... (Review)
Review
The mucus clearance system is the dominant mechanical host defense system of the human lung. Mucus is cleared from the lung by cilia and airflow, including both two-phase gas-liquid pumping and cough-dependent mechanisms, and mucus transport rates are heavily dependent on mucus concentration. Importantly, mucus transport rates are accurately predicted by the gel-on-brush model of the mucociliary apparatus from the relative osmotic moduli of the mucus and periciliary-glycocalyceal (PCL-G) layers. The fluid available to hydrate mucus is generated by transepithelial fluid transport. Feedback interactions between mucus concentrations and cilia beating, via purinergic signaling, coordinate Na absorptive vs Cl secretory rates to maintain mucus hydration in health. In disease, mucus becomes hyperconcentrated (dehydrated). Multiple mechanisms derange the ion transport pathways that normally hydrate mucus in muco-obstructive lung diseases, e.g., cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis (NCFB), and primary ciliary dyskinesia (PCD). A key step in muco-obstructive disease pathogenesis is the osmotic compression of the mucus layer onto the airway surface with the formation of adherent mucus plaques and plugs, particularly in distal airways. Mucus plaques create locally hypoxic conditions and produce airflow obstruction, inflammation, infection, and, ultimately, airway wall damage. Therapies to clear adherent mucus with hydrating and mucolytic agents are rational, and strategies to develop these agents are reviewed.
Topics: Cystic Fibrosis; Humans; Lung; Mucociliary Clearance; Mucus; Pulmonary Disease, Chronic Obstructive
PubMed: 35001665
DOI: 10.1152/physrev.00004.2021 -
The New England Journal of Medicine Dec 2010
Review
Topics: Asthma; Cystic Fibrosis; Humans; Lung Diseases; Mucociliary Clearance; Mucus; Pulmonary Disease, Chronic Obstructive; Respiratory Physiological Phenomena; Respiratory System
PubMed: 21121836
DOI: 10.1056/NEJMra0910061 -
Immunological Reviews Jul 2014The gastrointestinal tract is covered by mucus that has different properties in the stomach, small intestine, and colon. The large highly glycosylated gel-forming mucins... (Review)
Review
The gastrointestinal tract is covered by mucus that has different properties in the stomach, small intestine, and colon. The large highly glycosylated gel-forming mucins MUC2 and MUC5AC are the major components of the mucus in the intestine and stomach, respectively. In the small intestine, mucus limits the number of bacteria that can reach the epithelium and the Peyer's patches. In the large intestine, the inner mucus layer separates the commensal bacteria from the host epithelium. The outer colonic mucus layer is the natural habitat for the commensal bacteria. The intestinal goblet cells secrete not only the MUC2 mucin but also a number of typical mucus components: CLCA1, FCGBP, AGR2, ZG16, and TFF3. The goblet cells have recently been shown to have a novel gate-keeping role for the presentation of oral antigens to the immune system. Goblet cells deliver small intestinal luminal material to the lamina propria dendritic cells of the tolerogenic CD103(+) type. In addition to the gel-forming mucins, the transmembrane mucins MUC3, MUC12, and MUC17 form the enterocyte glycocalyx that can reach about a micrometer out from the brush border. The MUC17 mucin can shuttle from a surface to an intracellular vesicle localization, suggesting that enterocytes might control and report epithelial microbial challenge. There is communication not only from the epithelial cells to the immune system but also in the opposite direction. One example of this is IL10 that can affect and improve the properties of the inner colonic mucus layer. The mucus and epithelial cells of the gastrointestinal tract are the primary gate keepers and controllers of bacterial interactions with the host immune system, but our understanding of this relationship is still in its infancy.
Topics: Animals; Enterocytes; Gastrointestinal Tract; Goblet Cells; Humans; Immune System; Mucins; Mucous Membrane; Mucus; Peyer's Patches
PubMed: 24942678
DOI: 10.1111/imr.12182 -
Annals of the American Thoracic Society Nov 2018The lung is continuously exposed to particles, toxicants, and microbial pathogens that are cleared by a complex mechanical, innate, and acquired immune system.... (Review)
Review
The lung is continuously exposed to particles, toxicants, and microbial pathogens that are cleared by a complex mechanical, innate, and acquired immune system. Mucociliary clearance, mediated by the actions of diverse conducting airway and submucosal gland epithelial cells, plays a critical role in a multilayered defense system by secreting fluids, electrolytes, antimicrobial and antiinflammatory proteins, and mucus onto airway surfaces. The mucociliary escalator removes particles and pathogens by the mechanical actions of cilia and cough. Abnormalities in mucociliary clearance, whether related to impaired fluid secretion, ciliary dysfunction, lack of cough, or the disruption of epithelial cells lining the respiratory tract, contribute to the pathogenesis of common chronic pulmonary disorders. Although mucus and other airway epithelial secretions play a critical role in protecting the lung during acute injury, impaired mucus clearance after chronic mucus hyperproduction causes airway obstruction and infection, which contribute to morbidity in common pulmonary disorders, including chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis, cystic fibrosis, bronchiectasis, and primary ciliary dyskinesia. In this summary, the molecular and cellular mechanisms mediating airway mucociliary clearance, as well as the role of goblet cell metaplasia and mucus hyperproduction, in the pathogenesis of chronic respiratory diseases are considered.
Topics: Cell Differentiation; Cilia; Epithelial Cells; Humans; Lung Diseases; Mucins; Mucociliary Clearance; Mucus
PubMed: 30431340
DOI: 10.1513/AnnalsATS.201802-128AW -
Respiratory Care Oct 2013Disease processes can impair ciliary function, alter secretion production and mucus rheology, and interfere with the cough reflex. Airway clearance therapy has been a... (Review)
Review
Disease processes can impair ciliary function, alter secretion production and mucus rheology, and interfere with the cough reflex. Airway clearance therapy has been a cornerstone of therapy aimed at minimizing the devastating effects of airway obstruction, infection, and inflammation due to mucus stasis on the conducting airways and lung parenchyma. Although challenges to performing clinical studies evaluating the effectiveness of airway clearance therapeutic modalities exist, resources are available in the literature. In addition to device evaluations and original clinical research, the expert opinion, systematic reviews, and evidence-based practice guidelines can be found. These tools can be used to develop protocols and pathways to guide our practice. Monitoring and reporting patient, process, and financial outcomes are essential steps germane to the implementation of evidence-based care.
Topics: Airway Obstruction; Drainage, Postural; Humans; Mucociliary Clearance; Mucus; Respiratory Therapy
PubMed: 24064626
DOI: 10.4187/respcare.02590 -
Current Biology : CB Aug 2021Mucus is a slimy hydrogel that lines the mucosal surfaces in our body, including the intestines, stomach, eyes, lungs and urogenital tract. This glycoprotein-rich...
Mucus is a slimy hydrogel that lines the mucosal surfaces in our body, including the intestines, stomach, eyes, lungs and urogenital tract. This glycoprotein-rich network is truly the jack of all trades. As a barrier, it lubricates surfaces, protects our cells from physical stress, and selectively allows the passage of nutrients while clearing out pathogens and debris. As a home to our microbiota, it supports a level of microbial diversity that is unattainable with most culture methods. As a reservoir of complex carbohydrate structures called glycans, it plays critical roles in controlling cell adhesion and signaling, and it alters the behavior and spatial distribution of microbes. On top of all this, mucus regulates the passage of sperm during fertilization, heals wounds, helps us smell, and prevents the stomach from digesting itself, to name just a few of its functions. Given these impressive features, it is no wonder that mucus crosses boundaries of species and kingdoms - mucus gels are made by organisms ranging from the simplest metazoans to corals, snails, fish, and frogs. It is also no surprise that mucus is exploited in everyday applications, including foods, cosmetics, and other products relevant to medicine and industry.
Topics: Animals; Intestines; Microbiota; Mucous Membrane; Mucus; Nutrients
PubMed: 34375594
DOI: 10.1016/j.cub.2021.06.093 -
Brazilian Journal of Biology = Revista... Nov 2002The short length of the estrous cycle of rats makes them ideal for investigation of changes occurring during the reproductive cycle. The estrous cycle lasts four days...
The short length of the estrous cycle of rats makes them ideal for investigation of changes occurring during the reproductive cycle. The estrous cycle lasts four days and is characterized as: proestrus, estrus, metestrus and diestrus, which may be determined according to the cell types observed in the vaginal smear. Since the collection of vaginal secretion and the use of stained material generally takes some time, the aim of the present work was to provide researchers with some helpful considerations about the determination of the rat estrous cycle phases in a fast and practical way. Vaginal secretion of thirty female rats was collected every morning during a month and unstained native material was observed using the microscope without the aid of the condenser lens. Using the 10 x objective lens, it was easier to analyze the proportion among the three cellular types, which are present in the vaginal smear. Using the 40 x objective lens, it is easier to recognize each one of these cellular types. The collection of vaginal lavage from the animals, the observation of the material, in the microscope, and the determination of the estrous cycle phase of all the thirty female rats took 15-20 minutes.
Topics: Animals; Cervix Mucus; Estrous Cycle; Female; Rats; Rats, Wistar; Vaginal Smears
PubMed: 12659010
DOI: 10.1590/s1519-69842002000400008 -
Gut Microbes 2022The immune system in the large intestine is separated from commensal microbes and comparatively rare enteric pathogens by a monolayer of diverse epithelial cells... (Review)
Review
The immune system in the large intestine is separated from commensal microbes and comparatively rare enteric pathogens by a monolayer of diverse epithelial cells overlaid with a compact and adherent inner mucus layer and a looser outer mucus layer. Microorganisms, collectively referred to as the mucus-associated (MA) microbiota, physically inhabit this mucus barrier, resulting in a dynamic and incessant dialog to maintain both spatial segregation and immune tolerance. Recent major findings reveal novel features of the crosstalk between the immune system and mucus-associated bacteria in health and disease, as well as disease-related peripheral immune signatures indicative of host responses to these organisms. In this brief review, we integrate these novel observations into our overall understanding of host-microbiota mutualism at the colonic mucosal border and speculate on the significance of this emerging knowledge for our understanding of the prevention, development, and progression of chronic intestinal inflammation.
Topics: Colon; Gastrointestinal Microbiome; Humans; Immune System; Inflammation; Intestinal Mucosa; Mucus; Symbiosis
PubMed: 35239459
DOI: 10.1080/19490976.2022.2041342 -
International Journal of Molecular... Nov 2020Preterm births are a global health priority that affects 15 million babies every year worldwide. There are no effective prognostic and therapeutic strategies relating to... (Review)
Review
Preterm births are a global health priority that affects 15 million babies every year worldwide. There are no effective prognostic and therapeutic strategies relating to preterm delivery, but uterine infections appear to be a major cause. The vaginal epithelium is covered by the cervicovaginal mucus, which is essential to health because of its direct involvement in reproduction and functions as a selective barrier by sheltering the beneficial lactobacilli while helping to clear pathogens. During pregnancy, the cervical canal is sealed with a cervical mucus plug that prevents the vaginal flora from ascending toward the uterine compartment, which protects the fetus from pathogens. Abnormalities of the cervical mucus plug and bacterial vaginosis are associated with a higher risk of preterm delivery. This review addresses the current understanding of the cervicovaginal mucus and the cervical mucus plug and their interactions with the microbial communities in both the physiological state and bacterial vaginosis, with a focus on gel-forming mucins. We also review the current state of knowledge of gel-forming mucins contained in mouse cervicovaginal mucus and the mouse models used to study bacterial vaginosis.
Topics: Animals; Cervix Uteri; Female; Humans; Infectious Disease Transmission, Vertical; Mice; Microbiota; Mucins; Mucus; Pregnancy; Pregnancy Complications, Infectious; Vagina; Vaginosis, Bacterial
PubMed: 33158227
DOI: 10.3390/ijms21218266 -
Journal of the American Chemical Society Nov 2022Mucus hydrogels at biointerfaces are crucial for protecting against foreign pathogens and for the biological functions of the underlying cells. Since mucus can bind to... (Review)
Review
Mucus hydrogels at biointerfaces are crucial for protecting against foreign pathogens and for the biological functions of the underlying cells. Since mucus can bind to and host both viruses and bacteria, establishing a synthetic model system that can emulate the properties and functions of native mucus and can be synthesized at large scale would revolutionize the mucus-related research that is essential for understanding the pathways of many infectious diseases. The synthesis of such biofunctional hydrogels in the laboratory is highly challenging, owing to their complex chemical compositions and the specific chemical interactions that occur throughout the gel network. In this perspective, we discuss the basic chemical structures and diverse physicochemical interactions responsible for the unique properties and functions of mucus hydrogels. We scrutinize the different approaches for preparing mucus-inspired hydrogels, with specific examples. We also discuss recent research and what it reveals about the challenges that must be addressed and the opportunities to be considered to achieve desirable synthetic mucus hydrogels.
Topics: Hydrogels; Mucus; Bacteria
PubMed: 36074739
DOI: 10.1021/jacs.1c13547