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Showing papers on "Respiratory epithelium published in 1986"


Journal ArticleDOI
TL;DR: These and other findings suggest the hypothesis that the eosinophil mediates damage to the respiratory epithelium and is the prime effector cell in the pathophysiology of asthma.
Abstract: Eosinophilia of lung and blood associated with injury to the mucociliary escalator and excessive shedding of bronchial epithelium are hallmarks of both allergic and nonallergic asthma. In vitro, the eosinophil granule major basic protein (MBP) is toxic to helminths and to mammalian cells, including human respiratory epithelium. The MBP-mediated damage to the respiratory epithelium consists of desquamation and frank destruction of ciliated cells. Increased sputum MBP concentration is a good marker for asthma, and patients treated for acute asthma have high levels of MBP in their sputa, which decrease after treatment. Peak sputum MBP levels approximate concentrations toxic to respiratory epithelium in vitro. In the lungs of patients who had died of asthma, MBP has been localized outside of the eosinophil in association with damage to the epithelium. Overall, these and other findings suggest the hypothesis that the eosinophil mediates damage to the respiratory epithelium and is the prime effector cell in the pathophysiology of asthma.

612 citations


Journal ArticleDOI
TL;DR: It is concluded that CF airway epithelia absorb Na+ at an accelerated rate due to an abnormal CF beta receptor because similar effects were induced by forskolin, and because cAMP production was similar in normal and CF epithelium.
Abstract: The transepithelial potential difference (PD) of cystic fibrosis (CF) airway epithelium is abnormally raised and the Cl- permeability is low. We studied the contribution of active Na+ absorption to the PD and attempted to increase the Cl- permeability of CF epithelia. Nasal epithelia from CF and control subjects were mounted in Ussing chambers and were short-circuited. The basal rate of Na+ absorption was raised in CF polyps compared with control tissues. Whereas beta agonists induced Cl- secretion in normal and atopic epithelia, beta agonists further increased the rate of Na+ absorption in CF epithelia without inducing Cl- secretion. This unusual effect is not due to an abnormal CF beta receptor because similar effects were induced by forskolin, and because cAMP production was similar in normal and CF epithelia. We conclude that CF airway epithelia absorb Na+ at an accelerated rate. The abnormal response to beta agonists may reflect a primary abnormality in a cAMP-modulated path, or a normal cAMP-modulated process in a Cl- impermeable epithelial cell.

589 citations


Journal ArticleDOI
TL;DR: The respiratory tract contains dendritic cells that are capable of functioning in antigen presentation and that may be important in pulmonary immune responses.
Abstract: In this study, we identified a population of dendritic cells (DC) that exists throughout human and mouse pulmonary tissues, including the trachea, bronchi, alveoli, and visceral pleura. In human tissue, these DC were shown to be positive for HLA-DR and T200 antigens. In the mouse, the DC expressed not only Ia and the T200 antigen, but also Fc-IgG and C3bi receptors. Unlike alveolar macrophages, the DC were negative for nonspecific esterase staining and shared ultrastructural similarities with the DC described by Steinman (1), and with Langerhans' cells, even though they did not contain Birbeck granules. We were able to demonstrate that mouse pulmonary DC function in antigen presentation, as observed with the other DC. Thus, the respiratory tract contains DC that are capable of functioning in antigen presentation and that may be important in pulmonary immune responses.

372 citations


Journal ArticleDOI
TL;DR: It was concluded that under the conditions of the present study acetaldehyde is both cytotoxic and carcinogenic to the nasal mucosa of rats.

210 citations


Journal ArticleDOI
27 Jun 1986-Science
TL;DR: Results suggest that an anion-selective channel that was not strongly voltage-gated or regulated by calcium in cell-free patches is responsible for the apical chloride conductance in airway epithelia.
Abstract: The mechanism of chloride transport by airway epithelia has been of substantial interest because airway and sweat gland-duct epithelia are chloride-impermeable in cystic fibrosis. The decreased chloride permeability prevents normal secretion by the airway epithelium, thereby interfering with mucociliary clearance and contributing to the morbidity and mortality of the disease. Because chloride secretion depends on and is regulated by chloride conductance in the apical cell membrane, the patch-clamp technique was used to directly examine single-channel currents in primary cultures of human tracheal epithelium. The cells contained an anion-selective channel that was not strongly voltage-gated or regulated by calcium in cell-free patches. The channel was also blocked by analogs of carboxylic acid that decrease apical chloride conductance in intact epithelia. When attached to the cell, the channel was activated by isoproterenol, although the channel was also observed to open spontaneously. However, in some cases, the channel was only observed after the patch was excised from the cell. These results suggest that this channel is responsible for the apical chloride conductance in airway epithelia.

210 citations


Book ChapterDOI
01 Jan 1986
TL;DR: The respiratory epithelium forms a continuous layer of cells that separates air from liquid throughout the lung, which is a critical requirement for effective gas exchange, the uptake of O 2 from the environment and elimination of CO2 from the organism.
Abstract: The respiratory epithelium forms a continuous layer of cells that separates air from liquid throughout the lung. The integrity and function of the epithelium are a critical requirement for effective gas exchange, the uptake of O2 from the environment and elimination of CO2 from the organism. Transfer of gases between the air and the blood requires two anatomical structures: the conducting airways, which distribute the inspired air within the lungs, and the alveoli, which are the site of O2 and CO2 diffusion between the gas phase and the pulmonary capillary blood. The epithelia in both regions serve as passive barriers between gas and fluid phases and perform active ion transport functions. In the airways, the epithelium can actively secrete Cl- or absorb Na+; ion transport is an important determinant of the quantity and composition of the respiratory tract fluid, an essential component of mucociliary clearance. In the alveoli, the epithelium actively absorbs Na+; Na+ absorption is a major factor that maintains a fluid–free alveolus. In the fetal lung, the epithelium actively secretes Cl-; fluid secretion is a major requirement for normal pulmonary growth and development.

156 citations


Journal ArticleDOI
TL;DR: The results suggest that inhibitory and excitatory factor(s) are released from epithelial cells, and that these factors modulate the reactivity of the smooth muscle.

111 citations


Journal ArticleDOI
TL;DR: The distribution of nasal lesions induced by acetaldehyde correlated with regional aldehyde dehydrogenase deficiencies suggesting that regional susceptibility to the toxic effects of acetaldehyde may be due, at least in part, to a lack of aldehydes in the susceptible regions.

78 citations



Journal ArticleDOI
TL;DR: The respiratory epithelium of cystic fibrosis patients exhibits excessive sodium ( and volume) absorption and an absence of chloride (and volume) secretion in response to usual stimuli, and these abnormalities likely contribute to the pathophysiology of cysts fibrosis lung disease.

69 citations


Journal ArticleDOI
TL;DR: Results suggest that an anion channel that had a single channel conductance of approximately 29 pS at negative voltages in symmetrical 145 mmol/l Cl solutions may be responsible for the apical Cl conductance in canine tracheal epithelium.
Abstract: To investigate the cellular mechanism responsible for the apical membrane Cl conductance in airway epithelia, we used the patch-clamp technique to study single ion channels in primary cultures of canine tracheal epithelium. The cells contained an anion channel that had a single channel conductance of approximately 29 pS at negative voltages in symmetrical 145 mmol/l Cl solutions. In symmetrical Cl solutions the excised single-channel current-voltage relation was nonlinear, with conductance increasing at depolarizing voltages. The channel was inhibited by diphenylamine-2-carboxylate and anthracene-9-carboxylic acid at concentrations similar to those required to inhibit transepithelial Cl secretion. The channel was found in freshly isolated cells, isolated cells in culture, and in the apical membrane of confluent areas of cells. When attached to the cell the channel was activated by addition of isoproterenol in some, but not all cases. Often it was not observed to open until the patch was excised from the cell. The channel was not strongly voltage-gated, nor was it acutely regulated by internal Ca in the excised, inside-out configuration. These results suggest that this channel may be responsible for the apical Cl conductance in canine tracheal epithelium.

Journal Article
TL;DR: The tracheal epithelium of the ferret has few goblet cells while sero-mucous submucosal glands are present in large numbers throughout the length of the trachea and bronchi, and may well make a good model for the study of sub mucosal gland secretions.
Abstract: The tracheal epithelium of the ferret has few goblet cells while sero-mucous submucosal glands are present in large numbers throughout the length of the trachea and bronchi. The epithelium consists mainly of ciliated cells and of dark cytoplasmic non-ciliated cells that sometimes contain secretory granules. Any 'respiratory tract fluid' secreted into the ferret trachea is probably mainly glandular in origin. The epithelium contains neutrophils and a few mast cells and eosinophils. Nerve fibres are virtually absent from the epithelium, and this may be associated with a lack of the cough reflex from the ferret trachea. From a morphological point of view, the ferret trachea may well make a good model for the study of submucosal gland secretions.

Journal Article
TL;DR: Observations indicate that in addition to monocytes/macrophages IFN-gamma induces the expression of class II antigens on type II pneumocytes, which could not be localized at the ultrastructural level.

Book
01 Jan 1986
TL;DR: The role of vasoactive intestinal peptide (VIR) in asthma and the synthesis, release and effects of prostaglandins in the lung Platelets and aspirin-induced asthma PAF-acemer (platelet activating factor): an update Mast cell heterogeneity: an overview Nedocromil sodium (Tilade): a selective mucosal mast cell stabilizer.
Abstract: Mediators and inflammatory cells in asthma Allergen-induced late bronchial responses: physiologic and pharmacologic responses in the allergic sheep Experimental models of bronchial asthma in man and the rabbit Inflammatory cells and mediators in allergen-induced late-phase asthmatic reactions Bronchoalveolar lavage and the late asthmatic reaction Neuropeptides in the airways: functional significance The localization of neuropeptides in the mammalian respiratory tract The role of vasoactive intestinal peptide (VIR) in asthma Airways smooth muscle: an overview of morphology, electrophysiology and aspects of the pharmacology of contraction and relaxation Calcium ions and contraction of airways smooth muscle Calcium antagonists and airways smooth muscle Bronchodilator mechanisms Clinical applications of beta-agonists Beta-agonists as mast cell stabilizers Biological properties of lipoxygenase products: an overview Leukotrienes and asthma Leukotrienes and the upper airways The synthesis, release and effects of prostaglandins in the lung Platelets and aspirin-induced asthma PAF-acemer (platelet activating factor): an update Mast cell heterogeneity: an overview Nedocromil sodium (Tilade): a selective mucosal mast cell stabilizer Human bronchoalveolar mast cells and their mediators Histochemical aspects of the staining of mast cells with particular reference to heterogeneity and quantification Histamine release from human lung mast cells Glucocorticoid-resistant asthma: evidence for a defect in mononuclear cells Modes of administration of corticosteroids Inhibition by inhaled corticosteroid of bronchoconstriciton induced by allergen and exercise challenge tests Corticosteroids and leucocyte activation in chronic asthma Clinical patterns of responsiveness to corticosteroids Respiratory lining fluid Innervation of airway epithelium Heat loss, osmolarity and the respiratory epithelium.

Journal ArticleDOI
TL;DR: The epithelium appears not only to modulate the reactivity of the tissues to bronchoactive agents, but it also influences the magnitude of the contractile response following antigen challenge.

Journal ArticleDOI
TL;DR: The immunostaining has revealed the presence of the tartrate-resistant and vanadate-sensitive nucleotide phosphatase in many cells associated with tissue resorption and phagocytosis.
Abstract: Purified rabbit antiserum to a tartrate-resistant and vanadate-sensitive acid phosphatase (nucleotide tri- and diphosphatase) prepared from rat bone was used in immunocytochemical studies. The antigen was localized in sections of fixed, decalcified tissue (head from rat) using the peroxidase-antiperoxidase bridge (PAP) or the avidin-biotin-peroxidase complex (ABC) technique. Both techniques resulted in similar and specific immunostaining in the following cells and tissues: osteoclasts situated in resorption lacunae, epithelium overlying enamel-free areas of tips of cusps of unerupted molars, cilia of respiratory epithelium, and tissue macrophages. This distribution corresponds to the cellular sites of tartrate-resistant acid phosphatase activity, as revealed by enzyme histochemistry. With the ABC method, staining in osteoclasts was obtained with antiserum dilutions of up to 1:10,000. Biochemical studies revealed that vanadate-sensitive acid ATPase activity in liver subcellular fractions was almost exclusively confined to lysosomes. Thus, the immunostaining has revealed the presence of the tartrate-resistant and vanadate-sensitive nucleotide phosphatase in many cells associated with tissue resorption and phagocytosis.

Journal ArticleDOI
TL;DR: Two cystic lesions that were lined by pseudostratified ciliated columnar epithelium containing goblet cells are described in this article, and the proposed origin of these lesions is discussed.

Journal ArticleDOI
TL;DR: Results demonstrate that short-term exposure to 6 or 15 ppm of HCHO caused respiratory epithelial injury which was not cell specific, but was dose related in severity.

Journal ArticleDOI
TL;DR: Guinea pigs were more sensitive to the MIC vapor than were rats which were in turn more sensitive than mice, and these animals died shortly after exposure coupled with congestion, edema, and inflammation.

Journal ArticleDOI
TL;DR: Monoclonal antibodies were produced against isolated frog olfactory cilia, a preparation enriched in dendritic extensions of the chemosensory neurons, and two antibodies, 18.1 and 35.6, were found to react against specific glycoproteins of the sensory organelles.

Journal ArticleDOI
TL;DR: Inflammatory mediators, together with inflammatory cells, are important in the complex interactions involving airway epithelial cells, neutrophils, mast cells, smooth muscle, respiratory secretory cells, and nerves, which, in concert, are responsible for the pathophysiologic manifestations of obstructive lung disease.

Journal ArticleDOI
TL;DR: Three patients presented with orbital cysts lined with upper respiratory tract epithelium, and it is postulated that these cysts were caused by traumatic herniation of nasal sinus epithelia cells into the orbit.
Abstract: Three patients presented with orbital cysts lined with upper respiratory tract epithelium. In each case there was no evidence of an associated mucocele. Two patients had a past history of orbital trauma, and the third had had preceding sinus surgery. It is postulated that these cysts were caused by traumatic herniation of nasal sinus epithelium cells into the orbit.

Journal ArticleDOI
TL;DR: Observations were made by scanning and transmission electron microscopy on the migrating epithelial cells of the mouse rectum at intervals up to 24 h after stripping the epithelium off the mucosa to study the cells that are removed.
Abstract: Observations were made by scanning and transmission electron microscopy on the migrating epithelial cells of the mouse rectum at intervals up to 24 h after stripping the epithelium off the mucosa. Resurfacing of the denuded basal lamina proceeded by the centrifugal migration of the columnar cells of the crypts. Changes in these cells occurred very rapidly. In less than 20 min a flat leading lamella developed and extended out on the basal lamina. The leading lamella could be recognized easily in scanning electron micrographs by the absence of microvilli, although these were retained on the cell body, gradually getting less regular and sparser than normal. Many zeiotic blebs appeared on the free margin of these cells. The features of migrating epithelium which are displayed in the in vivo repair of rectal mucosa are shared with migrating epithelia cultured in vitro. Goblet cells appeared not to be active in resurfacing the lesions. They disappeared from the surface epithelium, but were evident again by 18 and 24 h. The method of producing these lesions can also be used to study the cells that are removed.

Journal ArticleDOI
TL;DR: The extent and ultrastructure of epithelium lining the transitional nasal mucosa of the neonate, gnotobiotic calf tissues were prepared for scanning and transmission electron microscopy and it was believed normally to occupy an extensive area of the nasal cavity.
Abstract: To determine the extent and ultrastructure of epithelium lining the transitional nasal mucosa of the neonate, gnotobiotic calf tissues were prepared for scanning and transmission electron microscopy. Stratified cuboid epithelium of the rostral 40% of the nasal cavity contained few ciliated cells; the next caudal 10-15%, although ciliated, had extensive nonciliated areas. The predominant type of surface cell was nonciliated, had short microvilli, and contained a multilobate nucleus and numerous pinocytotic vesicles. In some areas the surface of these cells presented a cobblestone appearance. Basal cells contained numerous bundles of filaments, ribosomes, and basal vesicles. Caudally, nonciliated columnar cells included a cell type similar to the more rostral cuboid cell, as well as brush cells and immature secretory and ciliated cells. Goblet cells were infrequently observed. Intraepithelial nerve terminals were abundant. Other intraepithelial cells, often difficult to identify owing to varying characteristics, included lymphocytes. Based upon comparisons of this neonatal epithelium with mature epithelium, observed in earlier studies of other mammalian species, the transitional mucosa is believed normally to occupy an extensive area of the nasal cavity.

Journal ArticleDOI
TL;DR: During the first postnatal week changes occurred that were related to the maturation of basal cells and secretory cells, especially in the ventral epithelium between the cartilage rings.
Abstract: The development of the tracheal epithelium was studied in neonatal hamsters beginning on the day of birth (day 1) and ending on day 8. Morphological changes were characterized and the proportions of cells (basal, secretory, ciliated) and mitotic indices were quantified along dorsal and ventral epithelial surfaces. Cellular proportions were stable throughout the week but the makeup of the dorsal and ventral epithelia was different. The ventral epithelium was composed of about 59% secretory cells, 39% basal cells, and 2% ciliated cells, whereas the dorsal epithelium was composed of about 52% secretory cells, 32% basal cells, and 16% ciliated cells. Mitotic indices were generally less than 1% and mitotic activity in secretory cells predominated proportionate to the ratios of secretory cells and basal cells in dorsal and ventral epithelia. During the first postnatal week changes occurred that were related to the maturation of basal cells and secretory cells. Glycogen was rapidly lost from both cell types during the first part of the week and the lateral cell membranes became increasingly complex. Apical microvilli had formed in the secretory cells by day 2 and hemidesmosomes were well developed in the basal cells. Rough and smooth endoplasmic reticulum membranes developed rapidly in the secretory cells, and mucous granules were abundant in some cells on days 4-8, especially in the ventral epithelium between the cartilage rings. The study shows that shifts in the proportions of basal, secretory, and ciliated cells do not occur in dorsal or ventral tracheal epithelium during the first postnatal week but the basal cells and secretory cells undergo rapid cytodifferentiation and functional maturation at this time.

Journal ArticleDOI
Gerald J. Gleich1
TL;DR: The possibility that the eosinophil is a major effector of the inflammation associated with asthma is discussed, and the pathology of asthma is characterized by mucus plugging of the bronchi and bronchioles.
Abstract: The pathology of asthma is characterized by mucus plugging of the bronchi and bronchioles, shedding of the respiratory epithelium with the formation of Creola bodies, denudation of the epithelium, the presence of necrotic eosinophilic material beneath the epithelium, a thickened basement membrane zone, bronchial smooth muscle hypertrophy, and goblet cell hyperplasia. In addition, pronounced tissue eosinophilia is present and Charcot-Leyden crystals may be present in sputum. Information linking the eosinophil to the pathophysiology of asthma is presented and the possibility that the eosinophil is a major effector of the inflammation associated with asthma is discussed.

Journal ArticleDOI
TL;DR: The hyperplastic nature of these carcinogen-induced lesions, together with the presence of cellular atypia and an altered involucrin distribution pattern, suggest a preneoplastic state.
Abstract: Repopulation of rat tracheas of human tracheobronchial epithelial cells obtained from intermediate autopsies was achieved by introducing into de-epithelialized rat tracheas either pieces of donor tissue containing respiratory mucosa or epithelial cells produced by an in vitro amplification of these cells. After tracheas were sealed, and transplanted into the subcutaneous tissues of nude mice, a newly formed epithelium migrated over the denuded luminal surface. During this process, regenerative epidermoid metaplasias, consisting of the growth of thin stratified epithelium with keratinization but without atypia was observed. Four weeks after xenotransplantation, most of the luminal surface was covered by columnar epithelium with occasional patches of epidermoid metaplasia. When this epithelium was exposed to 7,12-dimethylbenzo[a]anthracene (DMBA) a thick epidermoid metaplasia with mild to moderate atypia was observed. This type of epithelium is seen one to three months after insertion of the DMBA-containing pellets into the tracheal lumen. Immunohistochemical staining with antikeratin monoclonal antibodies AE1 and AE3 revealed increased immunostaining in both regenerative and DMBA-induced metaplasias compared with that of untreated normal mucociliary epithelium. Although no differences between the two types of metaplasias were detected with AE1 and AE3, the use of involucrin immunostain showed important differences. Normal respiratory epithelium did not contain involucrin, but this protein was seen in the surface layer of regenerative epidermoid metaplasias. In DMBA-induced metaplasias, involucrin was found not only in the superficial cells but was also present in numerous suprabasal cells. The hyperplastic nature of these carcinogen-induced lesions, together with the presence of cellular atypia and an altered involucrin distribution pattern, suggest a preneoplastic state.

Journal ArticleDOI
TL;DR: The radial arrangement of fibers, hemidesmosome rows, and corrugations is interpreted as a reflection of the continued centripetal migration of the epithelium.
Abstract: After corneas of mice had been totally denuded of their epithelium by the application of n-heptanol, the new epithelium which grew over the corneas was studied by electron microscopy at intervals up to 7 months. The purpose was to compare the basal attachment of the new cells, derived from conjunctiva, with that of true corneal epithelial cells growing on the same type of substratum, and studied previously.Goblet cells appeared after 2 weeks amid the squamous type of epithelial cells which had resurfaced the cornea in about 1 week. Goblet cells increased up to at least 6 weeks, but had decreased by 3 months. They persisted, however, for the entire 7 months of the study. Goblet cells had only a small area of contact with the basal lamina, and they had few desmosomes or hemidesmosomes.Basal cells of the squamous type had complex features of their basal attachment quite different from those of normal or repairing corneal epithelial cells studied previously. Flat cytoplasmic extensions of squamous cells under...

Journal ArticleDOI
TL;DR: This part of the paper will describe the ciliated epithelium of the tracheobronchial tract and its relation to vitamin A status.
Abstract: To estimate the role of vitamin A on ciliated cells we investigated whether ciliated cells undergo any alteration during vitamin A deficiency. The epithelia examined include the ciliated cells of the respiratory tract and the ciliated sensory cells of the inner ear, the tongue, and the olfactory cells. This part of the paper will describe the ciliated epithelium of the tracheobronchial tract and its relation to vitamin A status. During vitamin A deficiency a partial loss of ciliae can be observed before any squamous metaplasia (which usually occurs during longer lasting vitamin A deficiency) develops. The scanning electron microscopic data illustrate the altered surface of the epithelium during vitamin A deficiency better than transmission electron microscopy.

Journal Article
TL;DR: Results suggest that lack of beta 2-m, and presumably class I, may be a general phenotype of neuronal cells regardless of their mitotic state or exposure to environmental antigens.
Abstract: The olfactory neuroepithelium is unique in adult vertebrates in that bipolar sensory neurons are constantly dying and being replaced. The sensory neurons are also unusual because they are directly exposed to the external environment via their dendritic processes in the nasal cavity. Surveillance of this tissue by major histocompatibility complex (MHC) class I-restricted cytotoxic T cells would presumably serve as an important means of defense against foreign pathogens. Although adult brain shows a lack of class I molecules, it has not been reported if either proliferating neurons or sensory neurons in olfactory neuroepithelium also lack class I. To examine olfactory neuroepithelium, an antiserum against beta 2-microglobulin (beta 2-m), the invariant light chain associated with all class I molecules, was employed as a general probe in an immunocytochemical assay. beta 2-m was detected in columnar respiratory epithelium, blood vessel walls, and a small population of interstitial cells in the lamina propria, but no cell in the olfactory neuroepithelium stained for beta 2-m. Parallel patterns were obtained in the vomeronasal organ. These results suggest that lack of beta 2-m, and presumably class I, may be a general phenotype of neuronal cells regardless of their mitotic state or exposure to environmental antigens.