Showing papers on "Respiratory epithelium published in 1990"

Morphology of the human olfactory epithelium.

Abstract: The human olfactory epithelium has been previously studied with scanning electron microscopy; however, most studies have been limited to examining the epithelial surface. In an attempt to examine structures below the surface, we scanned epithelial fractures that occurred during tissue preparation. This made it possible to obtain unique three-dimensional images of cell profiles from the mucosal surface through the full depth of the epithelium. We examined supporting cells, olfactory neurons, basal cells, and a fourth cell type, the microvillar cell. Supporting cells had a microvillar surface and were in close contact with olfactory neurons and their processes. Olfactory neurons were primarily located in the middle and lower epithelial regions. Basal cells occurred alone or in clusters adjacent to the basal lamina. Microvillar cells were always observed in the upper epithelial region. They were flask- or pear-shaped, had a tuft of microvilli that extended into the nasal cavity, and a thin axon-like process that passed basally towards the lamina propria. This study represents the first comprehensive scanning electron microscopy examination of the human olfactory epithelium. Three-dimensional images obtained for each epithelial cell type allowed us to examine cell processes and their close contacts, especially between supporting cells and olfactory neurons. These results also revealed the irregular and patchy distribution of olfactory receptors within the human nasal cavity. Further studies that examine the detailed morphology of the human olfactory epithelium should provide a better understanding of the physiological mechanism and clinical disorders that affect olfactory function in humans.

Oxygen metabolites stimulate release of high-molecular-weight glycoconjugates by cell and organ cultures of rodent respiratory epithelium via an arachidonic acid-dependent mechanism.

Abstract: Several common pulmonary disorders characterized by mucus hypersecretion and airway obstruction may relate to increased levels of inhaled or endogenously generated oxidants (O2 metabolites) in the respiratory tract. We found that O2 metabolites stimulated release of high-molecular-weight glycoconjugates (HMG) by respiratory epithelial cells in vitro through a mechanism involving cyclooxygenase metabolism of arachidonic acid. Noncytolytic concentrations of chemically generated O2 metabolites (purine + xanthine oxidase) stimulated HMG release by cell and explant cultures of rodent airway epithelium, an effect which is inhibitable by coaddition of specific O2 metabolite scavengers or inhibitors of arachidonic acid metabolism. Addition of O2 metabolites to epithelial cells provoked production of PGF2a, an effect also inhibitable by coaddition of O2 metabolite scavengers or inhibitors of arachidonic acid metabolism. Finally, addition of exogenous PGF2a to cell cultures stimulated HMG release. We conclude that O2 metabolites increase release of respiratory HMG through a mechanism involving cyclooxygenase metabolism of arachidonic acid with production mainly of PGF2a. This mechanism may be fundamental to the pathogenesis of a variety of lung diseases associated with hypersecretion of mucus and/or other epithelial fluids, as well as a basic cellular response to increased oxidants.

A contiguous network of dendritic antigen-presenting cells within the respiratory epithelium.

Abstract: This study utilises a simple technique to section airway epithelium in a plane parallel to the basement membrane, thus providing a unique plan view of the intra-epithelial cell populations. Immunopero

Cis-acting sequences from a human surfactant protein gene confer pulmonary-specific gene expression in transgenic mice.

Abstract: Pulmonary surfactant is produced in late gestation by developing type II epithelial cells lining the alveolar epithelium of the lung. Lack of surfactant at birth is associated with respiratory distress syndrome in premature infants. Surfactant protein C (SP-C) is a highly hydrophobic peptide isolated from pulmonary tissue that enhances the biophysical activity of surfactant phospholipids. Like surfactant phospholipid, SP-C is produced by epithelial cells in the distal respiratory epithelium, and its expression increases during the latter part of gestation. A chimeric gene containing 3.6 kilobases of the promoter and 5'-flanking sequences of the human SP-C gene was used to express diphtheria toxin A. The SP-C-diphtheria toxin A fusion gene was injected into fertilized mouse eggs to produce transgenic mice. Affected mice developed respiratory failure in the immediate postnatal period. Morphologic analysis of lungs from affected pups showed variable but severe cellular injury confined to pulmonary tissues. Ultrastructural changes consistent with cell death and injury were prominent in the distal respiratory epithelium. Proximal components of the tracheobronchial tree were not severely affected. Transgenic animals were of normal size at birth, and structural abnormalities were not detected in nonpulmonary tissues. Lung-specific diphtheria toxin A expression controlled by the human SP-C gene injured type II epithelial cells and caused extensive necrosis of the distal respiratory epithelium. The absence of type I epithelial cells in the most severely affected transgenic animals supports the concept that developing type II cells serve as precursors to type I epithelial cells.

Localization of endothelin-like immunoreactivity in airway epithelium of rats and mice.

Abstract: We have examined lungs from adult Wistar rats (n = 6) and four different strains of juvenile and adult mice (n = 40) to localize endothelin-like immunoreactivity. Paraffin sections of lung tissue fixed by distension in Bouin's fluid were stained by the peroxidase-antiperoxidase (PAP) method using 10 different rabbit antisera to endothelin. Immunoreactivity was detected in the majority of epithelial cells of conducting airways from the hilum to the periphery and was similar in rats and all four strains of mice studied. Intense immunostaining was detected in mucous, serous and Clara cells and in occasional alveolar pneumocytes type II. Basal cells and most ciliated cells did not immunostain. From these results it is concluded that endothelin-like immunoreactivity is present in bronchiolar epithelial cells in vivo in rats and mice.

Cell Kinetics of Normal Adult Hamster Bronchial Epithelium in the Steady State

Abstract: To establish the progenitor role of bronchial epithelial cells in the steady state, we undertook a quantitative autoradiographic study in normal hamsters. Groups of 7 hamsters were killed 1 h and 1, 2, 3, 4, 7, and 14 d after an intraperitoneal injection of [3H]thymidine (2 microCi/g body wt). Autoradiograms were prepared from 861 Epon sections, 2 microns thick, of left intrapulmonary hilar bronchi. Epithelial cells were classified into 1 of 7 categories: basal-1 (B1) and basal-2 (B2), depending on nuclear height; secretory cells denoted as S1 with zero to 4 granules, S2 with 5 or more granules with intervening cytoplasm, and S3 with abundant granules completely filling the cytoplasm; ciliated (C); and indeterminate (IN). Mean silver grain counts decreased significantly over time only for B1 cells (P less than 0.05), with a cell cycle time of 20.6 d and a DNA synthetic time of 7.5 h. Labeled cells, 1 h after thymidine injection, comprised 30.5% S1, 27.8% B1, 22.8% B2, 6.8% IN, 6.4% S2, 5.7% C, and 0% S3 cells. Labeling indices of individual cell categories (LIc), at 1 h after labeling, were highest for B1 followed by B2 cells, reflecting their proliferative intensity. Labeling index of all epithelial cells combined did not change with time, indicating that there was no major cell death or label dilution. The LIc decreased significantly over time only for B1 and B2 cells (P less than 0.001 and P less than 0.002, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Dendritic cells in the respiratory tract.

Abstract: Studies from several laboratories on lung tissue samples from human and experimental animals have identified la+ cells with characteristic pleiomorphic (dendritic) morphology in the epithelium and underlying connective tissue, in both the conducting airways and in the distal lung. These dendritic cells (DC) are particularly prominent within the airway epithelium, forming a contiguous network equivalent to the Langerhans cells network of the epidermis. They may be readily concentrated from enzymatically disrupted respiratory tract tissue samples on the basis of their physical properties (notably non-adherence, lack of Fc-receptors and ultra-low density on percoll), and function as highly effective antigen presenting cells in vitro. Evidence is also accumulating that respiratory tract DC populations respond dynamically to local tissue inflammation, and as such may play a prominent role in immunoinflammatory disease processes in the airways and the distal lung.

Identification and biochemical analysis of novel olfactory-specific cytochrome P-450IIA and UDP-glucuronosyl transferase.

Abstract: Two major transmembranal polypeptides of bovine olfactory epithelium were identified by SDS electrophoretic analysis of Triton X-114 solubilized membranes. Both polypeptides were present in large amounts in membranes of the olfactory epithelium but were barely detectable in membranes of the nasal respiratory epithelium. Both polypeptides are enriched in the deciliated epithelium as compared with isolated cilia. One of them is a glycoprotein with an apparent molecular mass of 56 kDa (gp56); the other is an unglycosylated protein with an apparent molecular mass of 52 kDa (p52). Sequence analysis of peptides obtained by CNBr cleavage of purified gp56 indicates that it is highly homologous to UDP-glucuronosyl transferase (UDPGT). Parallel analysis shows that p52 is highly homologous to cytochrome P-450 sequences of the IIA subfamily. This protein is assigned the name P-450olf2. Polyclonal antibodies were raised against synthetic peptides corresponding to gp56 and p52 peptide sequences. Immunoblots with these antibodies reveal the following properties of gp56 and p52: (1) they are enriched in the microsomal fraction of the bovine olfactory epithelium; (2) they are possibly specific to the olfactory epithelium, as we could not detect reactivity in microsomes derived from respiratory epithelium or lung, and only a very small amount of basal reactivity was seen with liver microsomes; (3) cross-reacting proteins exist in microsomes derived from the rat olfactory epithelium. These results are consistent with a mechanism whereby the microsomal enzymes are involved in odorant modification and clearance from the nasal tissue.

Human Ciliated Bronchial Epithelial Cells: Expression of the HLA-DR Antigens and of the HLA-DR Alpha Gene, Modulation of the HLA-DR Antigens by Gamma-Interferon and Antigen-presenting Function in the Mixed Leukocyte Reaction

Abstract: HLA-DR class II molecules are expressed by a variety of nonlymphoid cells, including the respiratory epithelium. However, it is not known if ciliated bronchial epithelial cells express the HLA-DR genes, if the expression of class II molecules on their surface can be modulated by immune mediators and, finally, if these cells, like other HLA-DR-positive epithelial cells, have the potential to serve as antigen-presenting cells. To answer these questions, we collected ciliated bronchial epithelial cells by brushing and by suction during fiberoptic bronchoscopy and by scraping surgically resected bronchi. The number of cells recovered by brushing or suction during fiberoptic bronchoscopy was similar (P greater than 0.2), but lower than that obtained by scraping surgically resected bronchi (P less than 0.01); however, compared with brushing, suction of ciliated bronchial epithelial cells resulted in a better viability (P less than 0.05). HLA-DR antigens on ciliated bronchial epithelial cells were detected by immunofluorescence using the PTF 29.12 and the L243 monoclonal antibodies, both recognizing HLA-DR molecules on the vast majority of ciliated bronchial epithelial cells. Cytoplasmic dot blot analysis demonstrated that ciliated bronchial epithelial cells had mRNA HLA-DR transcripts, and Northern blot hybridizations showed that the size of the HLA-DR messages was the same observed in other HLA-DR-positive cells. Interestingly, ciliated bronchial epithelial cells showed a significant decline of HLA-DR expression after 5 days in culture, but the addition of gamma-interferon to the cell cultures was associated with the persistence of the expression of class II antigens on the cell surface (P less than 0.01 with control cultures at 5 days). Finally, while ciliated bronchial epithelial cells were ineffective in stimulating allogeneic T cell proliferation in a 6-day primary mixed leukocyte reaction (MLR), the addition of phorbol myristate acetate to the MLR was able to induce a significant T cell proliferation (P less than 0.001, all comparisons). Thus, human ciliated bronchial epithelial cells express HLA-DR surface antigens and have mRNA molecules for the HLA-DR genes, and the expression of the surface class II antigens can be modulated in vitro by immune mediators.(ABSTRACT TRUNCATED AT 400 WORDS)

The effects of activated eosinophils and neutrophils on guinea pig airway epithelium in vitro.

Abstract: Epithelial shedding is a characteristic feature of asthmatic airways and has been attributed to eosinophil products. We have examined the interaction of purified intraperitoneal guinea pig eosinophils with or without platelet-activating factor (PAF, 10(-7) M) or lyso-PAF (10(-7) M) with guinea pig tracheal epithelium in vitro. At 0, 4, 14, and 24 h, the percentage of ciliation of the tracheal circumference (CTC) was measured by light microscopy and the ciliary beat frequency (CBF) by photometry. PAF-activated eosinophils (50 x 10(6) cells/ml) disrupted the epithelium, mean CBF and CTC being reduced by 77.8 +/- 5.8% (mean +/- SEM; P less than 0.001 versus control) and 94.2 +/- 1.4% (P less than 0.001) over 24 h, respectively. PAF (10(-7) M) alone had no significant effect. Lyso-PAF with eosinophils (50 x 10(6) cells/ml) also reduced mean CBF and CTC but to a lesser extent. Eosinophils alone also led to a reduction of 36.2 +/- 11.4% in mean CBF and 53.0 +/- 15.5% in CTC, but these changes were not significant. The PAF antagonist, WEB 2086 (10(-6) M), significantly inhibited the mean CBF and CTC reduction due to PAF-activated eosinophils by 61.5 +/- 17.2% (P less than 0.01) and 20.8 +/- 6.5% (P less than 0.05), respectively. In addition, catalase (1,125 U/ml) partially inhibited the mean CBF and CTC reduction induced by PAF-activated eosinophils. Intraperitoneal neutrophils (PMN) (50 x 10(6) cells/ml) also disrupted epithelium but to a lesser extent (24-h reduction: 34.2 +/- 12.7% for mean CBF and 60.2 +/- 13.2% for CTC, respectively). Stimulation with PAF (10(-7) M) had no further effect. Marked exfoliation of the epithelial layer was observed after 14 h of incubation with activated eosinophils. We concluded the PAF-activated eosinophils are capable of grossly disrupting ciliated epithelium and may contribute to epithelial damage observed in asthma.

Peptidergic innervation of rat lymphoid tissue and lung: relation to mast cells and sensitivity to capsaicin and immunization.

Abstract: The peptidergic innervation of lymphoid tissue and the lung in relation to mast cells was studied in rat. The sensitivity of neuropeptide-containing nerves to capsaicin treatment and immunization was also examined. Measurements of the content of neurokinin A and calcitonin gene-related peptide revealed that the lung contained the highest content of both neuropeptides; lymph nodes had intermediate levels, whereas the spleen had the lowest content. Immunohistochemistry showed that the calcitonin gene-related peptide- and neurokinin A-immunoreactive nerves in lymph nodes were mainly found around blood vessels, whereas in the lung the nerves were present within the lining respiratory epithelium, bronchial smooth muscle, around blood vessels and close to lymphoid aggregates. Combined immunohistochemistry for serotonin (5-hydroxytryptamine), as a marker for mast cells, and tachykinins or calcitonin gene-related peptide revealed that a close association was often present between the nerves and 5-hydroxytryptamine-positive cells in the bronchi of the lung, while 5-hydroxytryptamine-positive cells were not observed in lymph nodes. The neurokinin A and calcitonin gene-related peptide content in lymph nodes, spleen and lung, but not the content of neuropeptide Y, was markedly decreased by capsaicin treatment, suggesting a sensory origin for the two former peptides. Aerosol immunization increased the levels of calcitonin gene-related peptide in the lung, whereas the content in mediastinal lymph nodes was not affected. These data demonstrate a peptidergic innervation mainly of blood vessels in lymphoid tissue and a close relation between sensory nerves and mast cells as well as lymphoid aggregates in the bronchi of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

The neutrophil and chronic allergic inflammation. Immunochemical localization of neutrophil elastase.

Abstract: To test whether neutrophils infiltrate and degranulate in areas of chronic respiratory allergic inflammation, we developed an indirect immunofluorescence technique to localize neutrophil elastase in formalin-fixed, paraffin-embedded tissues. The affinity-purified antielastase stained only neutrophils on peripheral blood buffy coat smears, and in lung tissue from patients with pneumonia. We examined tissue specimens from four patients with fatal asthma, 10 patients with chronic sinusitis, and 10 patients with nasal polyposis for the presence of elastase, as well as eosinophil granule major basic protein (MBP). Neutrophil infiltration and extracellular elastase deposition in association with damage to respiratory epithelium were generally sparse in most specimens; the exceptions were one patient with asthma, one patient with chronic sinusitis, and two patients with nasal polyposis. In contrast, eosinophil infiltration and extracellular MBP deposition were generally marked in most specimens; the exceptions were one patient with asthma and one patient with nasal polyps where extracellular MBP deposition did not coincide with damage to respiratory epithelium. The results suggest that the neutrophil does not usually infiltrate tissues showing allergic inflammation; however, on occasion, it may participate in these inflammatory reactions.

Origin and colocalization of CGRP- and SP-reactive nerves in cat airway epithelium

Abstract: A combination of neuroanatomic techniques was used to examine the origin and neuropeptide content of nerve fibers in the airway epithelium of adult cats. By the use of immunocytochemical methods, the peptides substance P (SP) and calcitonin gene-related peptide (CGRP) were colocalized in airway epithelial nerve fibers. Two days after wheat germ agglutinin (WGA) was injected into the nodose ganglion, fibers containing WGA immunoreactivity (IR) were detected in the airway epithelium. SP-like immunoreactivity (LI) and CGRP-LI were demonstrated separately in the WGA-IR fibers, establishing their origin from nerve cell bodies of nodose ganglion. Vagal transection inferior to the nodose ganglion reduced the number of SP- and CGRP-IR fibers by greater than 90% in ipsilateral airways. In contralateral airways, SP-IR fibers were substantially reduced, whereas the effect on CGRP-IR fibers was not statistically significant. Vagotomy superior to the nodose ganglion did not alter the density of peptide-IR fibers. The results prove that SP- and CGRP-IR nerve fibers of cat airway epithelium originate from nerve cell bodies in the nodose ganglion and that SP- and CGRP-like peptides may be stored together in some nerve fibers of the airway epithelium.

Epithelial modulation of airway smooth muscle.

Abstract: The responsiveness of airway smooth muscle is influenced by the functional integrity of the respiratory epithelium. The nature of this regulatory action by the epithelium remains largely unresolved. Several explanations may account for the epithelium-dependent responses induced by numerous stimuli. This review will present and discuss the evidence suggesting that the epithelium generates an inhibitory signal or signals that function to modulate the responsiveness of the underlying smooth muscle. In addition, the possible candidates for the identity of this epithelium-derived relaxing factor or factors will be assessed. Finally, the mechanisms by which the epithelium-derived relaxing factors may act to modulate bronchomotor tone will be discussed.

Duramycin enhances chloride secretion in airway epithelium.

Abstract: The effect of duramycin, a polypeptide antibiotic, on Cl- transport in canine tracheal epithelium mounted in Ussing chambers was studied. Over a narrow concentration range, duramycin increased shor...

Plasticity in the airway epithelium.

Abstract: Normal cell turnover as well as the response to injury require cell proliferation and differentiation. The airway epithelium maintains these processes throughout adult life. Controlled homeostatically, cell proliferation and differentiation usually restore, as an end point, the pseudostratified architecture of the normal mucociliary epithelium. After injury, however, cell proliferation and differentiation sometimes establish, as an end point, regions of metaplastic cells. In this brief review, we have tried to summarize research findings that 1) describe the development of metaplastic lesions in morphological terms, 2) identify cells the proliferation of which forms the basis of these lesions, and 3) identify molecular changes within these cells that control development of the metaplastic phenotype.

Immunoglobulin Secretion in the Airways

Abstract: Besides the gastrointestinal tract, the epithelial surface of the lung constitutes the next largest area that must be protected from invasion by microbes and toxic agents in the environment. Two principal mechanisms have evolved for the surveillance and protection of this epithelial boundary: One is relatively nonspecific and involves the mucociliary apparatus, which mechanically clears particles from the airways. The second is a more adaptive mechanism and involves the secretory immune system, which often operates in concert with the mucociliary escalator. Well before the recognition of the structure and function of antibodies, it was appreciated that specific neutralizing substances could be found in the secretions of the upper and lower respiratory tract that protected the host from a variety of infectious agents (e.g. influenza virus) (24, 66). Furthermore, these humoral responses to locally applied antigens could occur independently and often in the absence of systemic immunity. The next major advance was the recognition that the antibody responsible for this specific protection along the mucosal barrier was immunoglobulin A, 19A (61).

Immunochemical localization of Clara cell protein by light and electron microscopy in conducting airways of fetal and neonatal hamster lung.

Abstract: An antibody to a protein produced by Clara cells in adult Syrian golden hamsters has been used to monitor the development and functional differentiation of secretory cells in the conducting airway epithelium of this species. Lungs from fetal and neonatal hamsters at gestational day 11 and at intervals up to and including 3.5 weeks of age (as well as adults) were studied. The earliest time this Clara cell protein could be identified by immunoperoxidase labeling in the fetal conducting airways was at gestational day 15. On this day, labeling was observed in a few secretory cells lining the trachea, in many lining the lobar bronchi, and in virtually all secretory cells lining the bronchioles. Ciliated cells and endocrine cells were not labeled. Granules first appeared within the apical cytoplasm of the secretory cells on gestational day 15 at all airway levels. To identify the exact subcellular location of this protein, an ultrastructural labeling procedure using protein A gold was employed. The gold particles labeled only electron-dense granules within the secretory cells, indicating that they represent the specific site of this protein. Since secretory cells in the most distal conducting airways began to produce this protein on the same day in development as cells in the larger airways, including the trachea, this expression of functional maturation occurs simultaneously throughout the conducting respiratory tree rather than proceeding sequentially in a cranial to caudal direction. Consequently, secretory cells lining the smaller conducting airways mature more rapidly than those lining the larger airways.

Leukotriene d4 (ltd4) induces mucus secretion from goblet cells in the guinea pig respiratory epithelium

Abstract: To study the potential role of leukotriene (LTD4) as a mucus secretagogue, anesthetized and spontaneously breathing guinea pigs were intubated and challenged with various concentrations of an LTD4 aerosol. The resulting changes in airway resistance and compliance were then observed for 20 min, after which the animals were euthanized and the lower respiratory tract airways fixed for morphometric evaluation. Sections for these airways were stained with alcian blue-periodic acid Schiff (AB-PAS), photographed, and the content of AB-PAS positive granules in the epithelium of the extrapulmonary bronchi quantified. The fractional volume of mucus granules in the respiratory epithelial volume. Aerosol LTD4 produced a dose-dependent decrease in the granule fractional volume (GFV) over the range of 0.1 to 1 microgram/ml when compared with epithelia challenged with saline aerosols. Increasing the concentration of administered LTD4 from 1 microgram to 3 micrograms/ml produced further bronchoconstriction but had no further effect on the GFV. Decreases in GFV did not appear to be secondary to smooth muscle contraction since aerosols of other agonists (0.05% histamine and 1% acetylcholine), which yielded resistance changes similar to those of LTD4, did not effect the GFV. Pretreatment with an aerosol of the specific LTD4 receptor antagonist SK&F 104353-Z2 produced a dose-dependent inhibition of the changes in both the airway resistance and GFV. The data suggest that LTD4 mediates epithelial mucus secretion as well as bronchoconstriction in the guinea pig airway and may provide an additional therapeutic use for specific LTD4 receptor antagonists in the treatment of obstructive pulmonary disease.

Effects of epithelium removal on relaxation of airway smooth muscle induced by vasoactive intestinal peptide and electrical field stimulation.

Abstract: 1. We have studied the effect of epithelium removal on relaxation of guinea-pig isolated tracheal smooth muscle induced by vasoactive intestinal peptide (VIP) or stimulation of non-adrenergic, non-cholinergic (NANC) inhibitory nerves. Also examined were the effects of inhibitors of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE). 2. Epithelium removal produced a 3.6 +/- 0.4 fold leftward shift in the VIP concentration-response curve. The supersensitivity to VIP, following epithelium removal was abolished by phosphoramidon or thiorphan (NEP inhibitors), but unaffected by captopril (an ACE inhibitor). In intact trachea, the NEP inhibitors produced leftward shifts in the VIP curves similar to those produced by epithelium removal. 3. In contrast to responses to exogenous VIP, neurogenic NANC inhibitory responses to electrical field stimulation were affected neither by epithelial denudation nor by the peptidase inhibitors. 4. As in previous studies, epithelium removal increased tracheal sensitivity to isoprenaline. This was not altered by pretreatment with a cocktail of peptidase inhibitors. Thus, the effect of the NEP inhibitors on responses to VIP appears to be relatively specific. 5. These data indicate that exogenous VIP is a substrate for airway NEP, since inhibition of the enzyme potentiates the peptide. This is further evidence that the airway epithelium provides a source for the metabolism of mediators. 6. In guinea-pig trachea the NEP responsible for cleaving VIP may be located largely in the epithelial layer, since NEP inhibition was without effect on sensitivity to VIP in epithelium-denuded preparations. If VIP is a NANC inhibitory neurotransmitter in this tissue its degradation endogenously does not appear to involve epithelial NEP.

Effects of reversible nare occlusion on the development of the olfactory epithelium in the rabbit nasal septum.

Abstract: To investigate environmental influences on the development of the olfactory epithelium, semi-thin sections were taken from the nasal septum of newborn and 30-dayold rabbits; the epithelial thickness and the number of olfactory knobs, supporting cells, dark basal cells, and receptor cells were compared. During normal development, a marked increase in epithelial thickness was found, largely because of an increase in the number of receptor cells. Whereas unilateral nare occlusion on day 1 resulted in 10% fewer receptor cells and 25% fewer knobs on the deprived side by day 30, nare occlusion either up to or after day 5 had little effect, and even temporary reopening from days 6–7 was sufficient to stimulate receptor-cell development on the occluded side. Although in these latter cases, a slight deprivation effect of 6% was still found in the number of receptor-cell nuclei, there was no longer a significant difference in the number of knobs between the open and closed sides. Thus, whereas exposure to the environment during the first days of life appears to be sufficient to stimulate sustained growth, the deprived epithelium may retain the capacity to respond to such cues beyond this time. However, as nare occlusion also had an effect on the respiratory epithelium and nasal lymphatic tissue, the nature of the cues stimulating receptor-cell development, whether olfactory or non-olfactory, is not yet clear.

Modulation of bradykinin responses in airway smooth muscle by epithelial enzymes

Abstract: We have studied the effect of epithelium removal on responses of guinea pig trachea to bradykinin (BK). BK (1 nM–10 μM) gave a concentration-dependent relaxation when epithelium was present (E+: EC50=10±3 nM). Epithelium removal resulted in a biphasic response to BK with relaxation at low concentrations (E−: EC50=3.0±1.0 nM) and a recontraction to baseline at higher concentrations (EC50=2.0±1 μM). Phosphoramidon (10 μM), an inhibitor of neutral endopeptidase (NEP), which cleaves BK into inactive peptides, potentiated relaxation (EC50=1.0±0.9 nM and 0.1±0.1 nM in E+ and E respectively) and contraction in trachea with intact epithelium (EC50=0.08±0.03 μM). Inhibition of cyclooxygenase by indomethacin (5 μM), inhibited relaxation to BK in E+ tracheal segments, resulting in a slight contraction (EC50=1.0 μM), whereas a potent contractile response was observed in E−segments (EC50 1.6 μM, maximal contraction >1 g). In the presence of both indomethacin and phosphoramidon BK caused contraction, even in the presence of epithelium (EC50=0.2±0.11 μM), and the response in the absence of epithelium was similar to the response observed in trachea with intact epithelium (EC50=0.25±0.1 μM). The contractile effect of BK on airway smooth muscle may be inhibited by a protective role of epithelium, due to release of relaxant prostanoids and by degradation by epithelial NEP. In asthma, bronchoconstrictor responses to BK may be partly explained by loss of airway epithelium.