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1.
Microsc Res Tech ; 85(3): 1108-1119, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34761477

RESUMO

The current study was designed to give complete histo-and immunohistochemical features of the parabronchial epithelium of domestic fowl's (Gallus gallus domesticus) lung with special reference to Scanning electron microscope (SEM) and mean transmission electron microscope (TEM) features. The lung exhibited variable-sized atrial openings encircled by exchange tissue zones. The parabronchial atrial chambers appeared as ovoid and polygonal-shaped that separated by the well-developed interatrial septum. The deep atrial lumens had blood vessels pierced by openings that represent the infundibula. The parabronchial blood capillaries meshwork was branched and exhibited ovoid-shaped air capillaries with numerous extravasated blood vessels. By TEM, there were several air capillaries and groups of squamous and endothelial respiratory cells and the squamous cells had oval nucleus with evenly distributed chromatin. The endothelial respiratory cells had few microvilli on their free surfaces. The parabronchial tubes opened into a group of widened atria that had smooth muscle bundles at the interatrial septa. The atrial chambers led to narrow infundibula. Moreover, the lining epithelium of parabronchi, atria, infundibula, and air capillaries was formed by simple squamous epithelium. Air capillary walls were lined by two types of respiratory cells (Types-I and II). Collagen fibers were concentrated within the tunica externa layers of the parabronchial blood vessels as well as, they were observed in CT interparabronchial septa. Immunohistochemically, the elastin immunoreactivity was detected around the parabronchial blood vessels, at the base of each parabronchial atria, and in the area encircling the alveolar-capillary walls. Our work concluded that there are a relation between the fowl's lifestyle and the surrounding environmental conditions.


Assuntos
Brônquios , Galinhas , Animais , Brônquios/irrigação sanguínea , Brônquios/fisiologia , Brônquios/ultraestrutura , Elétrons , Epitélio , Pulmão/ultraestrutura , Microscopia Eletrônica de Transmissão , Aves Domésticas
2.
Int. j. morphol ; 39(2): 371-377, abr. 2021. ilus
Artigo em Inglês | LILACS | ID: biblio-1385372

RESUMO

SUMMARY: Diabetes mellitus increases the risk of developing chronic obstructive pulmonary disease (COPD). The small bronchiole is a prominent site of airflow obstruction that causes increased airway resistance in patients with the COPD. Therefore, the histological and ultrastructural changes in small bronchioles in streptozotocin (STZ)-induced chronic diabetes were determined. Twenty-four weeks after STZ induction, rats were sacrificed, and the right and left lungs were collected for examination by light and electron microscopy. The alterations to the small bronchioles were the same in both lungs of these diabetic rats. The bronchiolar epithelial cells, both ciliated and secretory club cells, showed pyknotic nuclei and damaged cytoplasmic organelles. Increased thickening of the bronchiolar wall occurred in diabetic rats due to smooth muscle layer thickening, inflammatory cell infiltration, and increased numbers of myofibroblasts with collagen deposition.These results indicated that chronic diabetes caused extreme damage to small bronchioles, which may lead to chronic small airway obstruction and ultimately increase the likelihood of COPD progression. This basic knowledge provides a better understanding of the progression of pathogenesis in the small airways of patients with prolonged diabetes.


RESUMEN: La diabetes mellitus aumenta el riesgo de desarrollar enfermedad pulmonar obstructiva crónica (EPOC). El bronquiolo es un sitio prominente de obstrucción del flujo de aire que causa una mayor resistencia de las vías respiratorias en pacientes con EPOC. Por lo tanto, se determinaron los cambios histológicos y ultraestructurales en los bronquiolos en la diabetes crónica inducida por estreptozotocina (STZ). 24 semanas después de la inducción de STZ, se sacrificaron las ratas y se analizaron los pulmones derecho e izquierdo por microscopía óptica y electrónica. Las alteraciones de los pequeños bronquiolos fueron las mismas en ambos pulmones de estas ratas diabéticas. Las células epiteliales bronquiolares, tanto ciliadas como secretoras, mostraban núcleos picnóticos y orgánelos citoplasmáticos dañados. Se produjo un aumento del engrosamiento de la pared bronquiolar en ratas diabéticas debido al engrosamiento de la capa de músculo liso, infiltración de células inflamatorias y un mayor número de miofibroblastos con colágeno. Estos resultados indicaron que la diabetes crónica causaba daño extremo a los pequeños bronquiolos, lo que puede conducir a una obstrucción crónica de las vías respiratorias pequeñas y además aumentar la probabilidad de progresión de la EPOC. Esta información proporcionará un mejor conocimiento de la patogénesis en las vías respiratorias pequeñas de los pacientes con diabetes prolongada.


Assuntos
Animais , Masculino , Ratos , Brônquios/patologia , Diabetes Mellitus Experimental/patologia , Brônquios/ultraestrutura , Doença Crônica , Ratos Sprague-Dawley , Microscopia Eletrônica de Transmissão
3.
J Med Microbiol ; 70(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33170120

RESUMO

Introduction. Infections with the respiratory pathogen Mycoplasma pneumoniae are often chronic, recurrent and resistant, persisting after antibiotic treatment. M. pneumoniae grown on glass forms protective biofilms, consistent with a role for biofilms in persistence. These biofilms consist of towers of bacteria interspersed with individual adherent cells.Hypothesis/Gap Statement. A tissue culture model for M. pneumoniae biofilms has not been described or evaluated to address whether growth, development and resistance properties are consistent with persistence in the host. Moreover, it is unclear whether the M. pneumoniae cells in the biofilm towers and individual bacterial cells have distinct roles in disease.Aim. We evaluated the properties of biofilms of M. pneumoniae grown on the immortalized human bronchial epithelial cell line BEAS-2B in relation to persistence in the host. We observed nucleation of biofilm towers and the disposition of individual cells in culture, leading to a model of how tower and individual cells contribute to infection and disease.Methodology. With submerged BEAS-2B cells as a substrate, we evaluated growth and development of M. pneumoniae biofilms using scanning electron microscopy and confocal laser scanning microscopy. We characterized resistance to erythromycin and complement using minimum inhibitory concentration assays and quantification of colony forming units. We monitored biofilm tower formation using time-lapse microscopic analysis of host-cell-free M. pneumoniae cultures.Results. Bacteria grown on host cells underwent similar development to those grown without host cells, including tower formation, rounding and incidence of individual cells outside towers. Erythromycin and complement significantly reduced growth of M. pneumoniae. Towers formed exclusively from pre-existing aggregates of bacteria. We discuss a model of the M. pneumoniae biofilm life cycle in which protective towers derive from pre-existing aggregates, and generate individual cytotoxic cells.Conclusion . M. pneumoniae can form protective biofilms in a tissue culture model, implicating biofilms in chronic infections, with aggregates of M. pneumoniae cells being important for establishing infections.


Assuntos
Biofilmes , Brônquios/microbiologia , Mycoplasma pneumoniae/fisiologia , Pneumonia por Mycoplasma/microbiologia , Antibacterianos/farmacologia , Brônquios/ultraestrutura , Linhagem Celular , Células Epiteliais/microbiologia , Células Epiteliais/ultraestrutura , Humanos , Microscopia Eletrônica de Varredura , Mycoplasma pneumoniae/efeitos dos fármacos , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/ultraestrutura
4.
Cell Rep Med ; 1(4): 100059, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32835306

RESUMO

In the current COVID-19 pandemic context, proposing and validating effective treatments represents a major challenge. However, the scarcity of biologically relevant pre-clinical models of SARS-CoV-2 infection imposes a significant barrier for scientific and medical progress, including the rapid transition of potentially effective treatments to the clinical setting. We use reconstituted human airway epithelia to isolate and then characterize the viral infection kinetics, tissue-level remodeling of the cellular ultrastructure, and transcriptional early immune signatures induced by SARS-CoV-2 in a physiologically relevant model. Our results emphasize distinctive transcriptional immune signatures between nasal and bronchial HAE, both in terms of kinetics and intensity, hence suggesting putative intrinsic differences in the early response to SARS-CoV-2 infection. Most important, we provide evidence in human-derived tissues on the antiviral efficacy of remdesivir monotherapy and explore the potential of the remdesivir-diltiazem combination as an option worthy of further investigation to respond to the still-unmet COVID-19 medical need.


Assuntos
Antivirais/farmacologia , Brônquios/virologia , Nariz/virologia , Mucosa Respiratória/virologia , SARS-CoV-2/efeitos dos fármacos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Remodelação das Vias Aéreas , Alanina/análogos & derivados , Alanina/farmacologia , Animais , Brônquios/efeitos dos fármacos , Brônquios/imunologia , Brônquios/ultraestrutura , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Chlorocebus aethiops , Diltiazem/farmacologia , Sinergismo Farmacológico , Humanos , Imunidade Inata , Modelos Biológicos , Nariz/efeitos dos fármacos , Nariz/imunologia , Nariz/ultraestrutura , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/imunologia , Mucosa Respiratória/ultraestrutura , SARS-CoV-2/crescimento & desenvolvimento , Células Vero , Tratamento Farmacológico da COVID-19
5.
Rev Mal Respir ; 37(3): 201-204, 2020 Mar.
Artigo em Francês | MEDLINE | ID: mdl-32139106

RESUMO

The main purpose of this review is to highlight mitochondria as a new therapeutic target to prevent bronchial smooth muscle (BSM) remodeling in asthma. Severe asthmatic patients, representing 5-10% of all asthmatics, are characterized by an increased BSM mass which is highly correlated with the severity of the disease and the rate of exacerbations. None of the current asthma therapies are effective in reducing BSM remodelling. This review, based on the current literature, reports the role of mitochondria in BSM, particularly in calcium signaling.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Brônquios , Mitocôndrias Musculares/efeitos dos fármacos , Terapia de Alvo Molecular/métodos , Animais , Antiasmáticos/administração & dosagem , Asma/metabolismo , Asma/patologia , Brônquios/citologia , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Brônquios/ultraestrutura , Sistemas de Liberação de Medicamentos/métodos , Metabolismo Energético/efeitos dos fármacos , Humanos , Mitocôndrias Musculares/metabolismo , Terapia de Alvo Molecular/tendências , Músculo Liso/citologia , Músculo Liso/efeitos dos fármacos , Músculo Liso/ultraestrutura , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/fisiologia , Terapias em Estudo/métodos , Terapias em Estudo/tendências
7.
Am J Physiol Lung Cell Mol Physiol ; 316(6): L990-L998, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30864819

RESUMO

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 (Untersuchungen uber den bau der Tracheo-Bronchial-Schleimhaut). 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 (Archiv für die gesamte Physiologie des Menschen und der Tiere 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.


Assuntos
Brônquios/ultraestrutura , Glândulas Exócrinas/ultraestrutura , Mucosa/ultraestrutura , Traqueia/ultraestrutura , Brônquios/anatomia & histologia , Brônquios/patologia , Epitélio/ultraestrutura , Glândulas Exócrinas/fisiologia , História do Século XIX , História do Século XX , Humanos , Mucosa/fisiologia , Muco/metabolismo , Traqueia/fisiologia
8.
Toxicol Sci ; 166(1): 51-64, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30010986

RESUMO

Occupational exposure to diesel exhaust may cause lung cancer in humans. Mechanisms include DNA-damage and inflammatory responses. Here, the potential of NIST SRM2975 diesel exhaust particles (DEP) to transform human bronchial epithelial cells (HBEC3) in vitro was investigated. Long-term exposure of HBEC3 to DEP led to increased colony growth in soft agar. Several DEP-transformed cell lines were established and based on the expression of epithelial-to-mesenchymal-transition (EMT) marker genes, one of them (T2-HBEC3) was further characterized. T2-HBEC3 showed a mesenchymal/fibroblast-like morphology, reduced expression of CDH1, and induction of CDH2 and VIM. T2-HBEC3 had reduced migration potential compared with HBEC3 and little invasion capacity. Gene expression profiling showed baseline differences between HBEC3 and T2-HBEC3 linked to lung carcinogenesis. Next, to assess differences in sensitivity to DEP between parental HBEC3 and T2-HBEC3, gene expression profiling was carried out after DEP short-term exposure. Results revealed changes in genes involved in metabolism of xenobiotics and lipids, as well as inflammation. HBEC3 displayed a higher steady state of IL1B gene expression and release of IL-1ß compared with T2-HBEC3. HBEC3 and T2-HBEC3 showed similar susceptibility towards DEP-induced genotoxic effects. Liquid-chromatography-tandem-mass-spectrometry was used to measure secretion of eicosanoids. Generally, major prostaglandin species were released in higher concentrations from T2-HBEC3 than from HBEC3 and several analytes were altered after DEP-exposure. In conclusion, long-term exposure to DEP-transformed human bronchial epithelial cells in vitro. Differences between HBEC3 and T2-HBEC3 regarding baseline levels and DEP-induced changes of particularly CYP1A1, IL-1ß, PGE2, and PGF2α may have implications for acute inflammation and carcinogenesis.


Assuntos
Poluentes Atmosféricos/toxicidade , Brônquios/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Material Particulado/toxicidade , Transcriptoma/efeitos dos fármacos , Emissões de Veículos/toxicidade , Brônquios/metabolismo , Brônquios/ultraestrutura , Técnicas de Cultura de Células , Linhagem Celular Transformada , Dano ao DNA , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Perfilação da Expressão Gênica , Humanos , Interleucina-1beta/genética
9.
Biochim Biophys Acta Biomembr ; 1860(5): 1143-1151, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29428502

RESUMO

The membrane skeleton forms a scaffold on the cytoplasmic side of the plasma membrane. The erythrocyte membrane represents an archetype of such structural organization. It has been documented that a similar membrane skeleton also exits in the Golgi complex. It has been previously shown that ßII spectrin and ankyrin G are localized at the lateral membrane of human bronchial epithelial cells. Here we show that protein 4.1N is also located at the lateral membrane where it associates E-cadherin, ß-catenin and ßII spectrin. Importantly, depletion of 4.1N by RNAi in human bronchial epithelial cells resulted in decreased height of lateral membrane, which was reversed following re-expression of mouse 4.1N. Furthermore, although the initial phase of lateral membrane biogenesis proceeded normally in 4.1N-depleted cells, the final height of the lateral membrane of 4.1N-depleted cells was shorter compared to that of control cells. Our findings together with previous findings imply that 4.1N, ßII spectrin and ankyrin G are structural components of the lateral membrane skeleton and that this skeleton plays an essential role in the assembly of a fully functional lateral membrane.


Assuntos
Brônquios/metabolismo , Proteínas do Citoesqueleto/fisiologia , Células Epiteliais/metabolismo , Microdomínios da Membrana/metabolismo , Proteínas de Membrana/fisiologia , Neuropeptídeos/fisiologia , Mucosa Respiratória/metabolismo , Animais , Brônquios/citologia , Brônquios/ultraestrutura , Comunicação Celular , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Células Cultivadas , Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/metabolismo , Células Epiteliais/ultraestrutura , Humanos , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Camundongos , Neuropeptídeos/química , Neuropeptídeos/metabolismo , Mucosa Respiratória/citologia , Mucosa Respiratória/ultraestrutura
10.
Sci Rep ; 8(1): 2447, 2018 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-29402960

RESUMO

Mucociliary clearance is a biomechanical mechanism of airway protection. It consists of the active transport along the bronchial tree of the mucus, a fluid propelled by the coordinated beating of a myriad of cilia on the epithelial surface of the respiratory tract. The physics of mucus transport is poorly understood because it involves complex phenomena such as long-range hydrodynamic interactions, active collective ciliary motion, and the complex rheology of mucus. We propose a quantitative physical analysis of the ciliary activity and mucus transport on a large panel of human bronchial cultures from control subjects, patients with asthma and chronic obstructive pulmonary disease obtained from endobronchial biopsies. Here we report on the existence of multiple ciliary domains with sizes ranging from the tens of a micron to the centimeter, where ciliary beats present a circular orientational order. These domains are associated with circular mucus flow patterns, whose size scales with the average cilia density. In these domains, we find that the radial increase of the ciliated cell density coupled with the increase in the orientational order of ciliary beats result in a net local force proportional to the mucus velocity. We propose a phenomenological physical model that supports our results.


Assuntos
Brônquios/ultraestrutura , Cílios/ultraestrutura , Depuração Mucociliar/fisiologia , Muco/fisiologia , Mucosa Respiratória/ultraestrutura , Asma/metabolismo , Asma/fisiopatologia , Fenômenos Biomecânicos , Brônquios/metabolismo , Brônquios/fisiopatologia , Broncoscopia , Estudos de Casos e Controles , Cílios/metabolismo , Cílios/patologia , Humanos , Hidrodinâmica , Modelos Biológicos , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/fisiopatologia , Reologia , Técnicas de Cultura de Tecidos
11.
Toxicol Lett ; 286: 108-119, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29309811

RESUMO

Polyhexamethylene guanidine (PHMG) has been widely used in the industry owing to its excellent biocidal, anti-corrosive, and anti-biofouling properties. In Korea, consumers exposed to PHMG-phosphate (PHMG-P)-containing humidifier disinfectant have begun to suffer from fibrotic lung injury-related symptoms for unknown reasons. However, no appropriate treatment has yet been found because the detail toxic mechanism has not been identified. Herein, we first studied the toxic mechanism of PHMG-P-containing solution using human normal bronchial epithelial cells (BEAS-2B cells). When exposed for 24 h, PHMG-P-containing solution rapidly decreased cell viability from around 6 h after exposure and significantly increased of the phosphatidylserine exposure and the LDH release. At 6 h of exposure, the material contained in the solution was found to be bound to the cell membrane and the inner wall of vacuoles, and damaged the cell membrane and organelles. In addition, a significant increase of IFN-γ was observed among cytokines, the expression of apoptosis-, autophagy-, and membrane and DNA damage-related proteins was also enhanced. Meanwhile, the level of intracellular ROS and the secretion of IL-8 and CXCL-1, which are chemokines for professional phagocytes, decreased. Thus, we treated dead BEAS-2B cells to lung fibroblasts (HFL-1), non-professional phagocytes, and then we observed that the dead cells rapidly attached to HFL-1 cells and were taken up. Additionally, increased secretion of IL-8 and CXCL-1 was observed in the cells. Based on these results, we suggest that pulmonary exposure to PHMG-P induces apoptosis of bronchial epithelial cells and lung fibroblasts might play an important role in the clearance of the apoptotic debris.


Assuntos
Apoptose/efeitos dos fármacos , Brônquios/efeitos dos fármacos , Citofagocitose , Desinfetantes/toxicidade , Células Epiteliais/efeitos dos fármacos , Fibroblastos/metabolismo , Guanidinas/toxicidade , Brônquios/metabolismo , Brônquios/ultraestrutura , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CXCL1/metabolismo , Relação Dose-Resposta a Droga , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Fibroblastos/ultraestrutura , Humanos , Interferon gama/metabolismo , Interleucina-8/metabolismo , L-Lactato Desidrogenase/metabolismo , Fosfatidilserinas/metabolismo , Fatores de Tempo
12.
Part Fibre Toxicol ; 13(1): 27, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27251132

RESUMO

BACKGROUND: Multi-walled carbon nanotubes (MWCNT) are currently under intense toxicological investigation due to concern on their potential health effects. Current in vitro and in vivo data indicate that MWCNT exposure is strongly associated with lung toxicity (inflammation, fibrosis, granuloma, cancer and airway injury) and their effects might be comparable to asbestos-induced carcinogenesis. Although fibrosis is a multi-origin disease, epithelial-mesenchymal transition (EMT) is recently recognized as an important pathway in cell transformation. It is known that MWCNT exposure induces EMT through the activation of the TGF-ß/Smad signalling pathway thus promoting pulmonary fibrosis, but the molecular mechanisms involved are not fully understood. In the present work we propose a new mechanism involving a TGF-ß-mediated signalling pathway. METHODS: Human bronchial epithelial cells were incubated with two different MWCNT samples at various concentrations for up to 96 h and several markers of EMT were investigated. Quantitative real time PCR, western blot, immunofluorescent staining and gelatin zymographies were performed to detect the marker protein alterations. ELISA was performed to evaluate TGF-ß production. Experiments with neutralizing anti-TGF-ß antibody, specific inhibitors of GSK-3ß and Akt and siRNA were carried out in order to confirm their involvement in MWCNT-induced EMT. In vivo experiments of pharyngeal aspiration in C57BL/6 mice were also performed. Data were analyzed by a one-way ANOVA with Tukey's post-hoc test. RESULTS: Fully characterized MWCNT (mean length < 5 µm) are able to induce EMT in an in vitro human model (BEAS-2B cells) after long-term incubation at sub-cytotoxic concentrations. MWCNT stimulate TGF-ß secretion, Akt activation and GSK-3ß inhibition, which induces nuclear accumulation of SNAIL-1 and its transcriptional activity, thus contributing to switch on the EMT program. Moreover, a significant increment of nuclear ß-catenin - due to E-cadherin repression and following translocation to nucleus - likely reinforces signalling for EMT promotion. In vivo results supported the occurrence of pulmonary fibrosis following MWCNT exposure. CONCLUSIONS: We demonstrate a new molecular mechanism of MWCNT-mediated EMT, which is Smad-independent and involves TGF-ß and its intracellular effectors Akt/GSK-3ß that activate the SNAIL-1 signalling pathway. This finding suggests potential novel targets in the development of therapeutic and preventive approaches.


Assuntos
Brônquios/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Mucosa Respiratória/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/agonistas , Animais , Brônquios/metabolismo , Brônquios/patologia , Brônquios/ultraestrutura , Testes de Carcinogenicidade , Linhagem Celular , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Exposição por Inalação/efeitos adversos , Masculino , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Nanotubos de Carbono/química , Nanotubos de Carbono/ultraestrutura , Tamanho da Partícula , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Mucosa Respiratória/ultraestrutura , Fatores de Transcrição da Família Snail/metabolismo , Propriedades de Superfície , Fator de Crescimento Transformador beta/metabolismo
13.
J Asthma ; 52(8): 785-94, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26194420

RESUMO

OBJECTIVE: Epidemiological studies have shown that elevated concentrations of ambient particulate matter (aerodynamic diameter ≤2.5 µm; PM2.5) correlates with increased incidence of asthma. The aim of this study was to determine whether PM2.5 participates in the exacerbation of asthma. METHODS: Effects of 1, 10 and 100 µg PM2.5 instilled intratracheally in ovalbumin (OVA)-sensitized or asthmatic mice were compared. RESULTS: PM2.5 exposure in the OVA-sensitized and especially asthmatic groups increased Mch responsiveness in a dose-dependent manner. In OVA-sensitized groups, exposure to 1 µg of PM2.5 caused no detectable lung inflammation, while 10 and 100 µg of PM2.5 resulted in a slightly increased trend in numbers of neutrophils and macrophages. Compared with the asthmatic control group, both 10 and 100 µg of PM2.5 provoked a significant increase in eosnophils and neutrophils whereas only 100 µg of PM2.5 noticeably enhanced lymphocytes. In asthmatic groups, administration of 100 µg of PM2.5 greatly increased levels of the pro-inflammatory cytokine TNF-α and Th2-related cytokines IL-4 and IL-10 in bronchoalveolar lavage fluid, but it decreased Th1-related INF-γ. In addition, 10 and 100 µg of PM2.5 exacerbated inflammatory infiltration, goblet cell metaplasia and lung ultrastructure lesions in asthmatic mice. CONCLUSIONS: Our results suggested that acute exposure of PM2.5 could synergize with allergens in the subsequent challenge to aggravate the severity of asthma in sensitized mice, possibly by promoting a Th2-biased immune response.


Assuntos
Poluentes Atmosféricos/toxicidade , Alérgenos , Asma/etiologia , Ovalbumina , Material Particulado/toxicidade , Animais , Asma/imunologia , Asma/patologia , Asma/fisiopatologia , Brônquios/patologia , Brônquios/ultraestrutura , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/imunologia , Feminino , Células Caliciformes/patologia , Contagem de Leucócitos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica
15.
Dis Model Mech ; 8(5): 487-99, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25762570

RESUMO

Mutations in the secreted glycoprotein ADAMTSL2 cause recessive geleophysic dysplasia (GD) in humans and Musladin-Lueke syndrome (MLS) in dogs. GD is a severe, often lethal, condition presenting with short stature, brachydactyly, stiff skin, joint contractures, tracheal-bronchial stenosis and cardiac valve anomalies, whereas MLS is non-lethal and characterized by short stature and severe skin fibrosis. Although most mutations in fibrillin-1 (FBN1) cause Marfan syndrome (MFS), a microfibril disorder leading to transforming growth factor-ß (TGFß) dysregulation, domain-specific FBN1 mutations result in dominant GD. ADAMTSL2 has been previously shown to bind FBN1 and latent TGFß-binding protein-1 (LTBP1). Here, we investigated mice with targeted Adamtsl2 inactivation as a new model for GD (Adamtsl2(-/-) mice). An intragenic lacZ reporter in these mice showed that ADAMTSL2 was produced exclusively by bronchial smooth muscle cells during embryonic lung development. Adamtsl2(-/-) mice, which died at birth, had severe bronchial epithelial dysplasia with abnormal glycogen-rich inclusions in bronchial epithelium resembling the cellular anomalies described previously in GD. An increase in microfibrils in the bronchial wall was associated with increased FBN2 and microfibril-associated glycoprotein-1 (MAGP1) staining, whereas LTBP1 staining was increased in bronchial epithelium. ADAMTSL2 was shown to bind directly to FBN2 with an affinity comparable to FBN1. The observed extracellular matrix (ECM) alterations were associated with increased bronchial epithelial TGFß signaling at 17.5 days of gestation; however, treatment with TGFß-neutralizing antibody did not correct the epithelial dysplasia. These investigations reveal a new function of ADAMTSL2 in modulating microfibril formation, and a previously unsuspected association with FBN2. Our studies suggest that the bronchial epithelial dysplasia accompanying microfibril dysregulation in Adamtsl2(-/-) mice cannot be reversed by TGFß neutralization, and thus might be mediated by other mechanisms.


Assuntos
Doenças do Desenvolvimento Ósseo/patologia , Brônquios/patologia , Epitélio/patologia , Proteínas da Matriz Extracelular/metabolismo , Deleção de Genes , Deformidades Congênitas dos Membros/patologia , Microfibrilas/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas ADAMTS , Animais , Animais Recém-Nascidos , Doenças do Desenvolvimento Ósseo/metabolismo , Brônquios/ultraestrutura , Microambiente Celular , Modelos Animais de Doenças , Epitélio/metabolismo , Epitélio/ultraestrutura , Matriz Extracelular/metabolismo , Fibrilina-1 , Fibrilina-2 , Fibrilinas , Glicogênio/metabolismo , Deformidades Congênitas dos Membros/metabolismo , Camundongos Endogâmicos C57BL , Ligação Proteica , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo
16.
Int. j. morphol ; 33(1): 267-274, Mar. 2015. ilus
Artigo em Inglês | LILACS | ID: lil-743796

RESUMO

The study was conducted on a total of three adult healthy freshly killed red foxes of both sexes weighing about 4-6 kg collected from Abou Rawwash, Giza, Egypt. The wall of trachea and bronchi formed of mucosa, submucosa and adventitia. The mucosa formed of pseudostratified columnar epithelium and lamina propria. The respiratory epithelium composed of tall columnar ciliated, goblet cells, basal cells, and neuroendocrine cells. Goblet cells account for about 20 to 30% of cells in the more proximal. Basal cells are relatively small triangular cells whose bases are attached to the basement membrane. The primary bronchiole is lined by simple columnar nonciliated to cuboidal epithelium containing some bronchiolar exocrine cells and some goblet cells. Neuroendocrine cells constitute about 4 to 5% of bronchial epithelial cells, attached at their bases to the basement membrane and have tapering apices. The lamina propria consists principally of a network of capillaries, a meshwork of connective tissue fibers continuous with the basement membrane. The submucosa formed of connective tissue elements and blood vessels and devoid of Tracheobronchial glands in red fox. The adventitia contain tracheal cartilage and muscle in trachea and bronchial cartilages and muscles in bronchi. Tracheal muscle is transverse bundles attached to the outer perichondrium. In the bronchi, muscle is organized in transverse bundles close to the epithelium adjacent to the lamina propria and longitudinal bundles close to the cartilages. Alveoli are demarcated by septa composed of a continuous layer of epithelial cells overlying a thin interstitium. The epithelial cells consist principally of type I and type II pneumocytes. SEM revealed that, the mucosal surface of both trachea and bronchi was completely covered by cilia. There were few glandular openings or goblet cell.


El estudio se realizó en tres zorros rojos adultos sanos, recién fallecidos, de ambos sexos, con un peso aproximado 4,6 kg recogidos de Abou Rawwash, Giza, Egipto. La pared de la tráquea y los bronquios estaban formados por mucosa, submucosa y adventicia. La mucosa estaba formada por un epitelio estratificado y lámina propia. El epitelio respiratorio ciliado compuesto de células caliciformes, células basales y células neuroendocrinas. Las células calciformes representaban alrededor del 20 al 30% de las células más proximales. Las células basales eran células triangulares relativamente pequeñas cuyas bases están unidas a la membrana basal. El bronquiolo principal está cubierto por un epitelio columnar simple no ciliado que contiene algunas células exocrinas bronquiolares y células caliciformes. Las células neuroendocrinas constituyen aproximadamente 4 a 5% de las células epiteliales bronquiales, unidas en sus bases a la membrana basal y tienen ápices de ahusamiento. La lámina propia consiste principalmente en una red de capilares, una malla de fibras de tejido conectivo continuo con la membrana basal. La submucosa formada por elementos del tejido conectivo y vasos sanguíneos y escasas glándulas traqueobronquiales. La capa adventicia contiene cartílago traqueal y muscular en la tráquea, y los bronquios cartílagos y músculos. En los bronquios, el músculo está compuesto de haces transversales cercanos al epitelio próximo a la lámina propia y haces longitudinales cerca de los cartílagos. Los alvéolos están delimitados por tabiques compuestos de una capa continua de células epiteliales que recubren un intersticio delgado. Las células epiteliales se componen principalmente de neumocitos tipo I y tipo II. El MEB reveló que la superficie de la mucosa de la tráquea y los bronquios estaba completamente cubierta por cilios. Se observaron pocas aberturas glandulares o células caliciformes.


Assuntos
Animais , Raposas/anatomia & histologia , Microscopia Eletrônica de Varredura , Sistema Respiratório/ultraestrutura , Brônquios/ultraestrutura , Alvéolos Pulmonares/ultraestrutura , Traqueia/ultraestrutura
17.
PLoS One ; 8(11): e78593, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24223826

RESUMO

Male cystic fibrosis (CF) patients survive longer than females and lung exacerbations in CF females vary during the estrous cycle. Estrogen has been reported to reduce the height of the airway surface liquid (ASL) in female CF bronchial epithelium. Here we investigated the effect of 17ß-estradiol on the airway surface liquid height and ion transport in normal (NuLi-1) and CF (CuFi-1) bronchial epithelial monolayers. Live cell imaging using confocal microscopy revealed that airway surface liquid height was significantly higher in the non-CF cells compared to the CF cells. 17ß-estradiol (0.1-10 nM) reduced the airway surface liquid height in non-CF and CF cells after 30 min treatment. Treatment with the nuclear-impeded Estrogen Dendrimer Conjugate mimicked the effect of free estrogen by reducing significantly the airway surface liquid height in CF and non-CF cells. Inhibition of chloride transport or basolateral potassium recycling decreased the airway surface liquid height and 17ß-estradiol had no additive effect in the presence of these ion transporter inhibitors. 17ß-estradiol decreased bumetanide-sensitive transepithelial short-circuit current in non-CF cells and prevented the forskolin-induced increase in ASL height. 17ß-estradiol stimulated an amiloride-sensitive transepithelial current and increased ouabain-sensitive basolateral short-circuit current in CF cells. 17ß-estradiol increased PKCδ activity in CF and non-CF cells. These results demonstrate that estrogen dehydrates CF and non-CF ASL, and these responses to 17ß-estradiol are non-genomic rather than involving the classical nuclear estrogen receptor pathway. 17ß-estradiol acts on the airway surface liquid by inhibiting cAMP-mediated chloride secretion in non-CF cells and increasing sodium absorption via the stimulation of PKCδ, ENaC and the Na(+)/K(+)ATPase in CF cells.


Assuntos
Brônquios/efeitos dos fármacos , Fibrose Cística/metabolismo , Células Epiteliais/efeitos dos fármacos , Estradiol/farmacologia , Mucosa Respiratória/efeitos dos fármacos , Sódio/metabolismo , Água/metabolismo , Amilorida/farmacologia , Brônquios/metabolismo , Brônquios/ultraestrutura , Bumetanida/farmacologia , Linhagem Celular , Colforsina/farmacologia , AMP Cíclico/metabolismo , Fibrose Cística/genética , Fibrose Cística/patologia , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Canais Epiteliais de Sódio/genética , Canais Epiteliais de Sódio/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Transporte de Íons/efeitos dos fármacos , Masculino , Ouabaína/farmacologia , Proteína Quinase C-delta/genética , Proteína Quinase C-delta/metabolismo , Mucosa Respiratória/metabolismo , Mucosa Respiratória/ultraestrutura , Transdução de Sinais , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismo
18.
Anat Rec (Hoboken) ; 296(11): 1768-74, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24106034

RESUMO

A transgenic ferret model of cystic fibrosis has recently been generated. It is probable that malfunction of airway mucous glands contributes significantly to the airway pathology of this disease. The usefulness of the ferret model may therefore depend in part on how closely the airway glands of ferrets resemble those of humans. Here, we show that in the ferret trachea glands are commonest in its most ventral aspect and disappear about half way up the lateral walls; they are virtually absent from the dorsal membranous portion. Further, the aggregate volume of glands per unit mucosal surface declines progressively by about 60% between the larynx and the carina. The average frequency of glands openings for the ferret trachea as a whole is only about one-fifth that in humans (where gland openings are found at approximately the same frequency throughout the trachea). Glands in the ferret trachea are on average about one-third the size of those in the human. Therefore, the aggregate volume of tracheal glands (per unit mucosal surface area) in the ferret is only about 6% that in humans. As in other mammalian species, airway glands in the ferret disappear at an airway internal diameter of ∼1 mm, corresponding approximately in this species to airway generation 6.


Assuntos
Brônquios/anatomia & histologia , Furões/anatomia & histologia , Mucosa/anatomia & histologia , Traqueia/anatomia & histologia , Animais , Brônquios/citologia , Brônquios/ultraestrutura , Fibrose Cística/patologia , Modelos Animais de Doenças , Feminino , Humanos , Microscopia Eletrônica de Varredura , Mucosa/citologia , Mucosa/ultraestrutura , Traqueia/citologia , Traqueia/ultraestrutura
19.
Ultrastruct Pathol ; 37(5): 312-7, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24047348

RESUMO

Respiratory syncytial virus (RSV) is a relevant agent of respiratory tract infections, especially in exacerbations of chronic lung diseases. Peribronchial submucosal glands are the main source of tracheobronchial mucus and therefore of major interest. The authors isolated and cultured human peribronchial gland cells and infected them with RSV. The course of infection was monitored by transmission electron, immuno-, and lectin fluorescence microscopy. Morphology shows virus factories with budding particles within cytoplasmatic vacuoles and virus release after 44 h of infection. Experimental infection of human peribronchial gland cells in primary culture appears to be a suitable model in pulmonary research.


Assuntos
Brônquios/ultraestrutura , Glândulas Exócrinas/ultraestrutura , Infecções por Vírus Respiratório Sincicial/patologia , Vírus Sincicial Respiratório Humano/ultraestrutura , Brônquios/virologia , Células Cultivadas , Glândulas Exócrinas/virologia , Imunofluorescência , Humanos , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/patogenicidade , Fatores de Tempo
20.
PLoS One ; 8(1): e54473, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23372732

RESUMO

We demonstrate the use of a high resolution form of optical coherence tomography, termed micro-OCT (µOCT), for investigating the functional microanatomy of airway epithelia. µOCT captures several key parameters governing the function of the airway surface (airway surface liquid depth, periciliary liquid depth, ciliary function including beat frequency, and mucociliary transport rate) from the same series of images and without exogenous particles or labels, enabling non-invasive study of dynamic phenomena. Additionally, the high resolution of µOCT reveals distinguishable phases of the ciliary stroke pattern and glandular extrusion. Images and functional measurements from primary human bronchial epithelial cell cultures and excised tissue are presented and compared with measurements using existing gold standard methods. Active secretion from mucus glands in tissue, a key parameter of epithelial function, was also observed and quantified.


Assuntos
Brônquios/ultraestrutura , Cílios/ultraestrutura , Células Epiteliais/ultraestrutura , Mucosa Respiratória/ultraestrutura , Tomografia de Coerência Óptica/instrumentação , Tomografia de Coerência Óptica/métodos , Animais , Brônquios/fisiologia , Cílios/fisiologia , Células Epiteliais/fisiologia , Humanos , Depuração Mucociliar/fisiologia , Muco/metabolismo , Cultura Primária de Células , Mucosa Respiratória/fisiologia , Suínos
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