-
Current Opinion in Structural Biology Apr 2023Contrary to first appearances, mucus structural biology is not an oxymoron. Though mucus hydrogels derive their characteristics largely from intrinsically disordered,... (Review)
Review
Contrary to first appearances, mucus structural biology is not an oxymoron. Though mucus hydrogels derive their characteristics largely from intrinsically disordered, heavily glycosylated polypeptide segments, the secreted mucin glycoproteins that constitute mucus undergo an orderly assembly process controlled by folded domains at their termini. Recent structural studies revealed how mucin complexes promote disulphide-mediated polymerization to produce the mucus gel scaffold. Additional protein-protein and protein-glycan interactions likely tune the mesoscale properties, stability, and activities of mucins. Evidence is emerging that even intrinsically disordered glycosylated segments have specific structural roles in the production and properties of mucus. Though soft-matter biophysical approaches to understanding mucus remain highly relevant, high-resolution structural studies of mucins and other mucus components are providing new perspectives on these vital, protective hydrogels.
Topics: Mucins; Mucus; Glycoproteins; Polysaccharides; Glycosylation
PubMed: 36753925
DOI: 10.1016/j.sbi.2022.102524 -
American Journal of Physiology. Lung... Oct 2019
Topics: Intubation, Intratracheal; Mucus; Respiratory System; Rheology
PubMed: 31508979
DOI: 10.1152/ajplung.00362.2019 -
Trends in Microbiology Nov 2021Efficient penetration of the mucus layer is needed for respiratory viruses to avoid mucociliary clearance prior to infection. Many respiratory viruses bind to glycans on... (Review)
Review
Efficient penetration of the mucus layer is needed for respiratory viruses to avoid mucociliary clearance prior to infection. Many respiratory viruses bind to glycans on the heavily glycosylated mucins that give mucus its gel-like characteristics. Influenza viruses, some paramyxoviruses, and coronaviruses avoid becoming trapped in the mucus by releasing themselves by means of their envelope-embedded enzymes that destroy glycan receptors. For efficient infection, receptor binding and destruction need to be in balance with the host receptor repertoire. Establishment in a novel host species requires resetting of the balance to adapt to the different glycan repertoire encountered. Growing understanding of species-specific mucosal glycosylation patterns and the dynamic interaction with respiratory viruses identifies the mucus layer as a major host-range determinant and barrier for zoonotic transfer.
Topics: Glycosylation; Host Specificity; Mucins; Mucus; Polysaccharides; Viruses
PubMed: 33875348
DOI: 10.1016/j.tim.2021.03.014 -
American Journal of Rhinology & Allergy Nov 2022Nasal mucus is proving to be a useful means by which to study the pathogenesis of chronic rhinosinusitis (CRS). Given the increase in publications examining nasal mucus... (Review)
Review
BACKGROUND
Nasal mucus is proving to be a useful means by which to study the pathogenesis of chronic rhinosinusitis (CRS). Given the increase in publications examining nasal mucus and the lack of a review on this topic, we will focus on this noninvasive approach to studying CRS. Particular attention will be drawn towards inflammatory cytokines and biomarkers and their influence on disease severity.
METHODS
A literature review of papers published in English pertaining to nasal mucus was performed using the PubMed database. The search utilized combinations of the following keywords: sinusitis, polyps, sample collection, nasal mucus, or nasal secretion. Studies solely on acute or bacterial sinusitis, allergic rhinitis, or cystic fibrosis were not included.
RESULTS
A wide variety of materials and methods have been used to collect nasal mucus. Numerous assay types have been performed with the most common being ELISA, cytometric bead array, and proteomics. Most studies have focused on examining the levels of Th1/Th2 cytokines along with chemokines associated with type 2 immunity. Other factors identified include growth factors, senescence-associated proteins, complement, and antimicrobial defenses have also been identified. Nasal mucus cytokines have proven useful in cluster analysis and predicting postoperative improvement in Sino-nasal Outcome Test (SNOT-22) scores. One limitation of the use of nasal mucus is that some studies have suggested that nasal mucus does not always reflect the tissue microenvironment.
CONCLUSIONS
Nasal mucus represents a critical tool by which to examine the sinonasal microenvironment in a noninvasive manner. Unlike studies of tissue, it can be utilized in both surgically and medically managed patients and avoids the trauma of biopsies. However, studies are still needed to determine the most effective method for nasal mucus collection. Studies should also take care to confirm that nasal mucus markers do, in fact, reflect the levels of the product studied in the tissue.
Topics: Biomarkers; Chronic Disease; Cytokines; Humans; Mucus; Nasal Polyps; Rhinitis; Sinusitis
PubMed: 35848564
DOI: 10.1177/19458924221111830 -
Human Vaccines & Immunotherapeutics Apr 2022In addition to the classical immunological functions such as neutralization, antibody-dependent cellular cytotoxicity, and complement activation, IgG antibodies possess... (Review)
Review
In addition to the classical immunological functions such as neutralization, antibody-dependent cellular cytotoxicity, and complement activation, IgG antibodies possess a little-recognized and under-utilized effector function at mucosal surfaces: trapping pathogens in mucus. IgG can potently immobilize pathogens that otherwise readily diffuse or actively swim through mucus by forming multiple low-affinity bonds between the array of pathogen-bound antibodies and the mucin mesh. Trapping in mucus can exclude pathogens from contacting target cells, and facilitate their rapid elimination by natural mucus clearance mechanisms. Despite the fact that most infections are transmitted at mucosal surfaces, this muco-trapping effector function has only been revealed within the past decade, with the evidence to date suggesting that it is a universal effector function of IgG-Fc capable of immobilizing both viral and highly motile bacterial pathogens in all major mucosal secretions. This review provides an overview of the current evidence for Fc-mucin crosslinking as an effector function for antibodies in mucus, the mechanism by which the accumulation of weak Fc-mucin bonds by IgG bound to the surface of a pathogen can result in immobilization of antibody-pathogen complexes, and how trapping in mucus can contribute to protection against foreign pathogens.
Topics: Antibody-Dependent Cell Cytotoxicity; Immunoglobulin G; Mucins; Mucus
PubMed: 34314289
DOI: 10.1080/21645515.2021.1939605 -
Inflammatory Bowel Diseases Nov 2014The intestinal epithelium is covered with mucus with the main structural building block being the densely O-glycosylated MUC2 mucin. The intestinal epithelium is exposed... (Review)
Review
The intestinal epithelium is covered with mucus with the main structural building block being the densely O-glycosylated MUC2 mucin. The intestinal epithelium is exposed to ingested material, our digestive machinery, and large amounts of microorganisms. Mucus is the first line of defense and aids to limit exposure to all these threats to the epithelium. In the small intestine, mucus acts as a matrix, which contains antimicrobial products, such as defensins and immunoglobulin A that limit epithelial exposure to the luminal bacteria. In the colon, the stratified inner mucus layer acts as a physical barrier excluding bacteria from the epithelium. Bacterial penetration of this normally restricted zone is observed in many colitis models and also in patients with ulcerative colitis. Mucus defects that allow bacteria to reach the epithelium and to stimulate an immune system response can lead to the development of intestinal inflammation. The current state of our knowledge concerning the function of the mucus layers and the main mucin component, MUC2, in inflammatory bowel disease is described in this review.
Topics: Animals; Humans; Inflammatory Bowel Diseases; Mucous Membrane; Mucus
PubMed: 25025717
DOI: 10.1097/MIB.0000000000000117 -
Trends in Molecular Medicine Jan 2022The prevalence of food allergies has reached epidemic levels but the cause remains largely unknown. We discuss the clinical relevance of the gut mucosal barrier as a... (Review)
Review
The prevalence of food allergies has reached epidemic levels but the cause remains largely unknown. We discuss the clinical relevance of the gut mucosal barrier as a site for allergic sensitization to food. In this context, we focus on an important but overlooked part of the mucosal barrier in pathogenesis, the glycoprotein-rich mucus layer, and call attention to both beneficial and detrimental aspects of mucus-gut microbiome interactions. Studying the intricate links between the mucus barrier, the associated bacteria, and the mucosal immune system may advance our understanding of the mechanisms and inform prevention and treatment strategies in food allergy.
Topics: Bacteria; Food Hypersensitivity; Gastrointestinal Microbiome; Humans; Intestinal Mucosa; Mucus
PubMed: 34810087
DOI: 10.1016/j.molmed.2021.10.004 -
Advanced Drug Delivery Reviews Jan 2018Although nanotechnology has been investigated during recent years to increase the bioavailability and therapeutic effects of mucosal administrated drugs, numerous... (Review)
Review
Although nanotechnology has been investigated during recent years to increase the bioavailability and therapeutic effects of mucosal administrated drugs, numerous barriers (e.g., pH environment, enzymes and mucus) still limit the delivery efficiency. And the epithelium would also affect the systemic mucosal drug delivery. Amongst all the barriers, the protective mucus has drawn more and more attention, which strongly hinders the accessibility of nanovehicles to epithelium. Therefore, trials to conquer the mucus barrier have been designed using two controversial strategies: mucoadhesion and mucus-penetration. This review summarizes the influence of mucus layer on nanomaterials and introduces the modification strategies by modulating surface properties (i.e., hydrophilicity/hydrophobicity and surface charge) to overcome mucus barriers. Furthermore, it also reviews advanced modification methods to meet the different surface requirements of nanovehicles to overcome mucus and epithelium barriers in systemic mucosal delivery.
Topics: Animals; Drug Carriers; Drug Delivery Systems; Humans; Mucus; Nanostructures; Surface Properties
PubMed: 28989056
DOI: 10.1016/j.addr.2017.10.001 -
Advanced Drug Delivery Reviews Jan 2018In this review we discuss mucus, the viscoelastic secretion from goblet or mucous producing cells that lines the epithelial surfaces of all organs exposed to the... (Review)
Review
In this review we discuss mucus, the viscoelastic secretion from goblet or mucous producing cells that lines the epithelial surfaces of all organs exposed to the external world. Mucus is a complex aqueous fluid that owes its viscoelastic, lubricating and hydration properties to the glycoprotein mucin combined with electrolytes, lipids and other smaller proteins. Electron microscopy of mucosal surfaces reveals a highly convoluted surface with a network of fibers and pores of varying sizes. The major structural and functional component, mucin is a complex glycoprotein coded by about 20 mucin genes which produce a protein backbone having multiple tandem repeats of Serine, Threonine (ST repeats) where oligosaccharides are covalently O-linked. The N- and C-terminals of this apoprotein contain other domains with little or no glycosylation but rich in cysteines leading to dimerization and further multimerization via SS bonds. The synthesis of this complex protein starts in the endoplasmic reticulum with the formation of the apoprotein and is further modified via glycosylation in the cis and medial Golgi and packaged into mucin granules via Ca bridging of the negative charges on the oligosaccharide brush in the trans Golgi. The mucin granules fuse with the plasma membrane of the secretory cells and following activation by signaling molecules release Ca and undergo a dramatic change in volume due to hydration of the highly negatively charged polymer brush leading to exocytosis from the cells and forming the mucus layer. The rheological properties of mucus and its active component mucin and its mucoadhesivity are briefly discussed in light of their importance to mucosal drug delivery.
Topics: Animals; Humans; Mucus
PubMed: 28970050
DOI: 10.1016/j.addr.2017.09.023 -
MicrobiologyOpen Feb 2022The search for new natural compounds for application in medicine and cosmetics is a trend in biotechnology. One of the sources of such active compounds is the snail...
The search for new natural compounds for application in medicine and cosmetics is a trend in biotechnology. One of the sources of such active compounds is the snail mucus. Snail physiology and the biological activity of their fluids (especially the mucus) are still poorly studied. Only a few previous studies explored the relationship between snails and their microbiome. The present study was focused on the biodiversity of the snail mucus used in the creation of cosmetic products, therapeutics, and nutraceuticals. The commonly used cultivation techniques were applied for the determination of the number of major bacterial groups. Fluorescence in situ hybridization for key taxa was performed. The obtained images were subjected to digital image analysis. Sequencing of the 16S rRNA gene was also done. The results showed that the mucus harbors a rich bacterial community (10.78 × 10 CFU/ml). Among the dominant bacteria, some are known for their ability to metabolize complex polysaccharides or are usually found in soil and plants (Rhizobiaceae, Shewanella, Pedobacter, Acinetobacter, Alcaligenes). The obtained data demonstrated that the snail mucus creates a unique environment for the development of the microbial community that differs from other parts of the animal and which resulted from the combined contribution of the microbiomes derived from the soil, plants, and the snails.
Topics: Amino Acid Sequence; Animals; Bacteria; Computational Biology; In Situ Hybridization, Fluorescence; Isoelectric Point; Metagenomics; Microbiota; Mucus; RNA, Ribosomal, 16S; Snails; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tandem Mass Spectrometry
PubMed: 35212476
DOI: 10.1002/mbo3.1263