Short-term whole body cigarette smoke exposure induces regional differences in cellular response in the mouse larynx
| Autor: | Elizabeth Erickson-DiRenzo, Meena Easwaran, Phillip A. Gall, Joshua D Martinez, Daniel J. Ramirez |
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| Rok vydání: | 2020 |
| Předmět: |
TPM
total particulate matter Larynx CO Carbon monoxide Necrosis Health Toxicology and Mutagenesis BrdU 5-bromo-2′-deoxyuridine CS cigarette smoke 010501 environmental sciences Toxicology BLOQ below limits of quantitation 01 natural sciences NMR nicotine metabolite ratio PAHs polycyclic aromatic hydrocarbons RA1190-1270 Cell proliferation AB/PAS Alcian blue/Periodic acid Schiff CBF ciliary beat frequency RE respiratory epithelium 0303 health sciences REV reversibility CC3 cleaved caspase-3 Cigarette smoke Regular Article H&E Hematoxylin and Eosin SWGTOX Scientific Working Group for Forensic Toxicology MMAD Mass median aerodynamic diameter Murine larynx SCIREQ Scientific Respiratory Equipment Inc medicine.anatomical_structure TSNA tobacco-specific nitrosamines medicine.symptom SSE stratified squamous epithelium Cell death VSC veterinary service center Mucus production Surface topography Andrology 03 medical and health sciences ROS reactive oxygen species MCC mucociliary clearance medicine CSE cigarette smoke exposure SEM scanning electron microscopy Subglottis ComputingMethodologies_COMPUTERGRAPHICS 030304 developmental biology 0105 earth and related environmental sciences VF vocal fold DAB 3 3′-diaminobenzidine TBST tris-buffered saline-tween 20 business.industry HPF high power field Mucin FTC/ISO Federal Trade Commission/International Standard Organization GSD geometric standard deviation HIER heat-induced antigen retrieval Epithelium Apoptosis Toxicology. Poisons Respiratory epithelium BSA bovine serum albumin OECD organization for economic co-operation and development business UPLC-MS/MS ultra-performance liquid chromatography-tandem mass spectrometer Respiratory tract |
| Zdroj: | Toxicology Reports, Vol 8, Iss, Pp 920-937 (2021) Toxicology Reports |
| ISSN: | 2214-7500 |
| Popis: | Graphical abstract Highlights • Short-term CSE induced regional differences in murine laryngeal cellular responses. • Basal cell hyperplasia accompanies adaptive cell proliferation in the vocal folds. • Increased subglottic cell proliferation persists even after CS cessation. • SEM revealed vocal fold microprojection damage with possible necrotic features. • Subglandular acidic mucins decreased and neutral mucins increased post-CSE. The larynx is an essential organ in the respiratory tract and necessary for airway protection, respiration, and phonation. Cigarette smoking is a significant risk factor associated with benign and malignant laryngeal diseases. Despite this association, the underlying mechanisms by which cigarette smoke (CS) drives disease development are not well elucidated. In the current study, we developed a short-term murine whole body inhalation model to evaluate the first CS-induced cellular responses in the glottic [i.e. vocal fold (VF)] and subglottic regions of the larynx. Specifically, we investigated epithelial cell proliferation, cell death, surface topography, and mucus production, at various time points (1 day, 5 days, 10 days) after ∼ 2 h exposure to 3R4F cigarettes (Delivered dose: 5.6968 mg/kg per cigarette) and following cessation for 5 days after a 5 day CS exposure (CSE). CSE elevated levels of BrdU labeled proliferative cells and p63 labeled epithelial basal cells on day 1 in the VF. CSE increased proliferative cells in the subglottis at days 5, 10 and following cessation in the subglottis. Cleaved caspase-3 apoptotic activity was absent in VF at all time points and increased at day 1 in the subglottis. Evaluation of the VF surface by scanning electron microscopy (SEM) revealed significant epithelial microprojection damage at day 10 and early signs of necrosis at days 5 and 10 post-CSE. SEM visualizations additionally indicated the presence of deformed cilia at days 5 and 10 after CSE and post-cessation in the respiratory epithelium lined subglottis. In terms of mucin content, the impact of short-term CSE was observed only at day 10, with decreasing acidic mucin levels and increasing neutral mucin levels. Overall, these findings reveal regional differences in murine laryngeal cellular responses following short-term CSE and provide insight into potential mechanisms underlying CS-induced laryngeal disease development. |
| Databáze: | OpenAIRE |
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