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Development (Cambridge, England) Oct 2019The upper airway epithelium, which is mainly composed of multiciliated, goblet, club and basal cells, ensures proper mucociliary function and can regenerate in response...
The upper airway epithelium, which is mainly composed of multiciliated, goblet, club and basal cells, ensures proper mucociliary function and can regenerate in response to assaults. In chronic airway diseases, defective repair leads to tissue remodeling. Delineating key drivers of differentiation dynamics can help understand how normal or pathological regeneration occurs. Using single-cell transcriptomics and lineage inference, we have unraveled trajectories from basal to luminal cells, providing novel markers for specific populations. We report that: (1) a precursor subgroup of multiciliated cells, which we have entitled deuterosomal cells, is defined by specific markers, such as DEUP1, FOXN4, YPEL1, HES6 and CDC20B; (2) goblet cells can be precursors of multiciliated cells, thus explaining the presence of hybrid cells that co-express markers of goblet and multiciliated cells; and (3) a repertoire of molecules involved in the regeneration process, such as keratins or components of the Notch, Wnt or BMP/TGFβ pathways, can be identified. Confirmation of our results on fresh human and pig airway samples, and on mouse tracheal cells, extend and confirm our conclusions regarding the molecular and cellular choreography at work during mucociliary epithelial differentiation.
Topics: Animals; Cell Differentiation; Cells, Cultured; Epithelial Cells; Goblet Cells; Humans; Mice; RNA-Seq; Respiratory Mucosa; Swine; Trachea
PubMed: 31558434
DOI: 10.1242/dev.177428 -
Developmental Biology Jul 2019The terminal cells of the tracheal epithelium in Drosophila melanogaster are one of the few known cell types that undergo subcellular morphogenesis to achieve a stable,... (Review)
Review
The terminal cells of the tracheal epithelium in Drosophila melanogaster are one of the few known cell types that undergo subcellular morphogenesis to achieve a stable, branched shape. During the animal's larval stages, the cells repeatedly sprout new cytoplasmic processes. These grow very long, wrapping around target tissues to which the terminal cells adhere, and are hollowed by a gas-filled subcellular tube for oxygen delivery. Our understanding of this ramification process remains rudimentary. This review aims to provide a comprehensive summary of studies on terminal cells to date, and attempts to extrapolate how terminal branches might be formed based on the known genetic and molecular components. Next to this cell-intrinsic branching mechanism, we examine the extrinsic regulation of terminal branching by the target tissue and the animal's environment. Finally, we assess the degree of similarity between the patterns established by the branching programs of terminal cells and other branched cells and tissues from a mathematical and conceptual point of view.
Topics: Animals; Drosophila melanogaster; Larva; Organogenesis; Respiratory Mucosa; Trachea
PubMed: 30529233
DOI: 10.1016/j.ydbio.2018.12.001 -
In Vivo (Athens, Greece) 2022Allicin has been known to improve wound healing via antimicrobial and anti-inflammatory properties. The aim of this study was to evaluate whether an allicin-coated...
BACKGROUND/AIM
Allicin has been known to improve wound healing via antimicrobial and anti-inflammatory properties. The aim of this study was to evaluate whether an allicin-coated tracheal tube can prevent tracheal stenosis through improving wound healing after tracheal injury.
MATERIALS AND METHODS
Allicin-coated silicone tracheal tube (t-tube) was prepared by the polydopamine-mediated coating method. Tracheal mucosa was injured, and an allicin-coated t-tube was placed into the trachea to evaluate mucosal changes until designated time point. Anti-inflammatory, anti-bacterial and cytotoxic effects of allicin were also investigated in in vitro.
RESULTS
Allicin- coated silicone was not cytotoxic, and it showed anti-inflammatory and anti-bacterial effects in in vitro analysis. The use of allicin-coated t-tube in a rabbit model showed favorable mucosal healing with significant decrease of proinflammatory cytokines compared to the non-coated tube group. The allicin-coated tube showed obvious decreased number of cocci-shaped bacterial attached to the tube surface. From the histological point of view, the allicin- coated tube showed faster regeneration of the normal respiratory epithelial structure compared to the non-coated group.
CONCLUSION
Allicin-coated t-tube showed anti-inflammatory and anti-bacterial effects on injured tracheal mucosa. We suggest that allicin-coated t-tube can be used for promoting physiological wound healing to prevent laryngotracheal stenosis.
Topics: Animals; Anti-Inflammatory Agents; Bacteria; Disulfides; Mucous Membrane; Rabbits; Sulfinic Acids; Trachea; Tracheal Stenosis
PubMed: 35478119
DOI: 10.21873/invivo.12819 -
Tissue Engineering and Regenerative... Apr 2021Long segmental tracheal repair is challenging in regenerative medicine due to low adhesion of stem cells to tracheal scaffolds. Optimal transplantation of stem cells for...
BACKGROUND
Long segmental tracheal repair is challenging in regenerative medicine due to low adhesion of stem cells to tracheal scaffolds. Optimal transplantation of stem cells for tracheal defects has not been established. We evaluated the role of hyaluronic acid (HA) coating of tracheal scaffolds in mesenchymal stem cell (MSC) adhesion and tracheal regeneration in a rabbit model.
METHODS
A three-dimensionally printed tubular tracheal prosthesis was incubated with dopa-HA-fluorescein isothiocyanate in phosphate-buffered saline for 2 days. MSCs were incubated with an HA-coated scaffold, and their adhesion was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. HA coated scaffolds with or without MSC seeding were transplanted at the circumferential tracheal defect in rabbits, and survival, rigid bronchoscopy, radiologic findings, and histologic findings were compared between the two groups.
RESULTS
HA-coated scaffolds showed better MSC adhesion than non-coated scaffolds. The HA-coated scaffolds with MSC group showed a wider airway and greater mucosal regeneration compared to the HA-coated scaffolds without MSC group.
CONCLUSION
HA coating of scaffolds can promote MSC adhesion and tracheal regeneration.
Topics: Animals; Hyaluronic Acid; Mesenchymal Stem Cells; Rabbits; Regeneration; Tissue Scaffolds; Trachea
PubMed: 33765289
DOI: 10.1007/s13770-021-00335-2 -
Clinical and Experimental Allergy :... Sep 1995
Review
Topics: Animals; Bronchi; Cell Membrane Permeability; Epithelium; Guinea Pigs; Humans; Nasal Mucosa; Respiratory Physiological Phenomena; Trachea
PubMed: 8564718
DOI: 10.1111/j.1365-2222.1995.tb00022.x -
The Annals of Otology, Rhinology, and... Feb 2017Complete separation of upper and lower respiratory tract after total laryngectomy results in permanent effects on nasal cavities and tracheo-bronchial airways. Aim of...
OBJECTIVE
Complete separation of upper and lower respiratory tract after total laryngectomy results in permanent effects on nasal cavities and tracheo-bronchial airways. Aim of this study is evaluating nasal and tracheal cytological alterations of mucosa in laryngectomy long-term survivors, analyzing the feasibility of scraping for cytological examination of tracheal mucosa.
METHODS
Twenty-five laryngectomy patients underwent symptoms' evaluation, endoscopic fiber optic examination, prick tests, and nasal and tracheal scraping for cytological exam. Twenty-five healthy subjects underwent the same assessment, except for tracheal scraping. Eleven laryngectomy patients accepted inferior turbinate biopsy for histological examination.
RESULTS
Nasal cytological analysis demonstrated mucous cell metaplasia in 20% of laryngectomized patients, but it was absent in all healthy subjects; no squamous cell metaplasia was found in both groups. In 15 patients (60%), bacteria were present, without inflammatory infiltrate. Tracheal cytological analysis demonstrated a quite high rate of squamous cell metaplasia (24%), neutrophilic infiltrate (32%), and presence of bacteria (40%). Histological examination of inferior turbinate showed submucosal stromal fibrosis in all patients and submucosal inflammatory infiltrate in 1 case (9%).
CONCLUSION
Nasal cavities and trachea of laryngectomy patients undergo long-term cytological and histological changes of mucosa and submucosa, probably due to airflow modifications.
Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Case-Control Studies; Epithelial Cells; Female; Goblet Cells; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Laryngectomy; Male; Metaplasia; Middle Aged; Nasal Mucosa; Respiratory Mucosa; Squamous Cell Carcinoma of Head and Neck; Survivors; Trachea
PubMed: 27831517
DOI: 10.1177/0003489416676500 -
American Journal of Physiology. Lung... Jun 2019This historical article provides a comprehensive review of early research on the structure and function of airway submucosal glands. The literature before 1950 or so, is... (Review)
Review
This historical article provides a comprehensive review of early research on the structure and function of airway submucosal glands. The literature before 1950 or so, is virtually unknown, but in addition to being of historical interest it contains much of relevance to current research. Airway glands were first mentioned in 1602. The first description of their general form, size, and distribution was in 1712. Gland morphology was determined in 1827 by injecting mercury into their openings. Wax was later used. Detailed comparative information for all regions of the tracheobronchial tree was provided by Frankenhauser in 1879 (). Histological studies began in 1870, and by the end of the 19th century, all the major histological features had been described. The first physiological studies on airway mucous secretion were published in 1892. Kokin, in 1896 ( 63: 622-630), was the first to measure secretion from individual glands. It was not, however, until 1933 that gland secretion was quantified. This early literature raises important questions as to the role of the collecting duct epithelium in modifying primary secretions. It also provides perhaps the most accurate measure of basal gland secretion in vivo.
Topics: Bronchi; Epithelium; Exocrine Glands; History, 19th Century; History, 20th Century; Humans; Mucous Membrane; Mucus; Trachea
PubMed: 30864819
DOI: 10.1152/ajplung.00068.2019 -
Ear, Nose, & Throat Journal Dec 2022Necrotizing tracheitis is a rare condition, mainly seen in immunocompromised patients, that may lead to pseudomembrane formation, airway obstruction and in severe cases,...
Necrotizing tracheitis is a rare condition, mainly seen in immunocompromised patients, that may lead to pseudomembrane formation, airway obstruction and in severe cases, tracheal perforation. We present a case of a 32-year-old male with poorly controlled diabetes who presented with productive cough, dysphagia, and respiratory distress. Bronchoscopy revealed extensive tracheal necrosis along a 4-5 cm segment of cartilaginous trachea and was complicated by tracheal perforation with false passage into the anterior mediastinum. Once the airway was re-established, a multidisciplinary team discussed options for definitive airway management, including tracheal reconstruction, pulmonary stent, or tracheostomy. Ultimately, a distal XLT tracheostomy was placed. Microbiology specimens of the tracheal tissue were positive for . The patient was started on long-term antibiotics and diabetes management. At three-month follow-up, the trachea was patent with near complete mucosalization of the previously necrotic segment. An area of proximal tracheal stenosis was successfully managed with a customized tracheal T-tube. In conclusion, this is a case of necrotizing tracheitis complicated by tracheal perforation. Successful treatment required a multidisciplinary team for airway management as well as medical treatment of immunocompromising risk factors and antimicrobial therapy. This enabled timely healing of the trachea and a durable airway.
Topics: Humans; Male; Adult; Tracheitis; Trachea; Tracheal Diseases; Bacterial Infections; Tracheostomy; Anti-Bacterial Agents
PubMed: 36028929
DOI: 10.1177/01455613221123664 -
Glycobiology Jul 2017Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation...
Siglecs are transmembrane sialoglycan binding proteins, most of which are expressed on leukocyte subsets and have inhibitory motifs that translate cell surface ligation into immune suppression. In humans, Siglec-8 on eosinophils, mast cells and basophils and Siglec-9 on neutrophils, monocytes and some T-cells, mediate immune cell death, inhibition of immune mediator release and/or enhancement of anti-inflammatory mediator release. Endogenous sialoglycan ligands in tissues, mostly uncharacterized, engage siglecs on leukocytes to inhibit inflammation. Glycan array analyses demonstrated that Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E (respectively) have distinct glycan binding specificities, with Siglec-8 more structurally restricted. Since siglecs are involved in lung inflammation, we studied Siglec-8 and Siglec-9 ligands in human lungs and airways. Siglec-8 ligands are in tracheal submucosal glands and cartilage but not airway epithelium or connective tissues, whereas Siglec-9 ligands are broadly distributed. Mouse airways do not have Siglec-8 ligands, whereas Siglec-9 ligands are on airways of both species. Extraction of human airways and lung followed by electrophoretic resolution and siglec blotting revealed Siglec-8 ligands in extracts of human trachea and cultured tracheal gland cells, but not parenchyma or cultured airway epithelial cells whereas Siglec-9 ligands were extracted from all airway and lung tissues and cells tested. Siglec-8 and Siglec-9 ligands in airways appear to be high molecular weight O-linked sialoglycoproteins. These data reveal differential glycan specificities of Siglec-8, Siglec-9 and their mouse counterparts Siglec-F and Siglec-E, and the tissue distributions and molecular characteristics of Siglec-8 and Siglec-9 sialoglycan ligands on human airways and lungs.
Topics: Adult; Antigens, CD; Antigens, Differentiation, B-Lymphocyte; Cells, Cultured; Female; Humans; Lectins; Ligands; Lung; Male; Middle Aged; N-Acetylneuraminic Acid; Polysaccharides; Protein Binding; Respiratory Mucosa; Sialic Acid Binding Immunoglobulin-like Lectins; Trachea
PubMed: 28369504
DOI: 10.1093/glycob/cwx026 -
The Laryngoscope Jul 2021Glutamine inhibition has been demonstrated an antifibrotic effect in iatrogenic laryngotracheal stenosis (iLTS) scar fibroblasts in vitro. We hypothesize that broadly...
OBJECTIVE/HYPOTHESIS
Glutamine inhibition has been demonstrated an antifibrotic effect in iatrogenic laryngotracheal stenosis (iLTS) scar fibroblasts in vitro. We hypothesize that broadly active glutamine antagonist, DON will reduce collagen formation and fibrosis-associated gene expression in iLTS mice.
STUDY DESIGN
Prospective controlled animal study.
METHODS
iLTS in mice were induced by chemomechanical injury of the trachea using a bleomycin-coated wire brush. PBS or DON (1.3 mg/kg) were administered by intraperitoneal injection (i.p.) every other day. Laryngotracheal complexes were harvested at days 7 and 14 after the initiation of DON treatment for the measurement of lamina propria thickness, trichrome stain, immunofluorescence staining of collagen 1, and fibrosis-associated gene expression.
RESULTS
The study demonstrated that DON treatment reduced lamina propria thickness (P = .025) and collagen formation in trichrome stain and immunofluorescence staining of collagen 1. In addition, DON decreased fibrosis-associated gene expression in iLTS mice. At day 7, DON inhibited Col1a1 (P < .0001), Col3a1 (P = .0046), Col5a1 (P < .0001), and Tgfβ (P = .023) expression. At day 14, DON reduced Co1a1 (P = .0076) and Tgfβ (P = .023) expression.
CONCLUSIONS
Broadly active glutamine antagonist, DON, significantly reduces fibrosis in iLTS mice. These results suggest that the concept of glutamine inhibition may be a therapeutic option to reduce fibrosis in the laryngotracheal stenosis.
LEVEL OF EVIDENCE
N/A Laryngoscope, 131:E2125-E2130, 2021.
Topics: Animals; Bleomycin; Collagen; Diazooxonorleucine; Disease Models, Animal; Fibroblasts; Fibrosis; Gene Expression; Glutamine; Iatrogenic Disease; Injections, Intraperitoneal; Laryngostenosis; Mice; Mucous Membrane; Prospective Studies; Trachea; Tracheal Stenosis
PubMed: 33433011
DOI: 10.1002/lary.29385