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PubMed2000

Muscarinic control of histamine release from airways. Inhibitory M1-receptors in human bronchi but absence in rat trachea.

Isolated human bronchi and rat tracheae were incubated in organ baths to measure histamine release. The calcium ionophore A23187, 3 micromol/L in rat trachea and 10 micromol/L in human bronchi, stimulated histamine release by 145 +/- 50% (n = 6) and 270 +/- 48% (n = 7) above the prestimulation level, respectively. Acetylcholine (100 pmol/L; human bronchi) or oxotremorine (1, 100, 10,000 nmol/L; rat trachea) did not affect the spontaneous histamine release. In rat tracheae neither acetylcholine nor oxotremorine inhibited A23187-evoked histamine release, whereas 100 pmol/L acetylcholine significantly suppressed the evoked histamine release in human bronchi by 86%. For receptor characterization the following subtype-specific muscarinic receptor antagonists were applied: pirenzepine (M1 subtype), para-fluorohexahydrosiladifendiol (pFHHSiD; similar affinities at human cloned M1-, M3-, and M4-receptors), AF-DX 116 (M2 subtype), and clozapine (antagonist at cloned M1-, M2-, M3-receptors; agonist at cloned M4-receptors). Pirenzepine, pFHHSiD, AF-DX 116, and clozapine (100 nmol/L each) antagonized the inhibitory effect of 100 pmol/L acetylcholine by 83 +/- 20% (n = 6), 83 +/- 9% (n = 8), 50 +/- 14% (n = 6), and 35 +/- 7% (6). In conclusion, a species difference exists in the cholinergic control of histamine release between human and rat airways. In human airways muscarinic receptors most likely of the M1 subtype are involved in the inhibitory control of mast cell function, whereas such an inhibitory pathway does not exist in the rat trachea.

Acetylcholine↗
PubMed1994

Recombinant stem cell factor-induced mast cell activation and smooth muscle contraction in human bronchi.

The effect of human recombinant stem cell factor (SCF) on inflammatory mediator release and smooth muscle contraction was evaluated in human isolated intralobar bronchi. Bronchi from 21 of 26 donors contracted in response to SCF. The threshold concentration was approximately 0.01 micrograms/ml. At 1 micrograms/ml, the tissues contracted to about 60% of the carbamylcholine-induced maximum contraction. The responses to SCF mimicked those obtained with anti-IgE. Thus, the contractions to SCF and anti-IgE were inhibited to a similar extent by a combination of a cysteinyl-leukotriene receptor antagonist and a histamine H1 receptor antagonist. SCF also mimicked the effect of anti-IgE in releasing histamine, i-LTD4, and PGD2 from the bronchi. At a threshold concentration for contraction (0.01 micrograms/ml), SCF had no effect on subsequent responses to anti-IgE in the bronchi. The data suggest that human recombinant SCF contracts airway smooth muscle by stimulating the release of contractile mediators from bronchial mast cells. The data fail to support the hypothesis that SCF primes bronchial mast cells to subsequent immunologic stimuli.

Antibodies, Anti-Idiotypic↗
PubMed2005

beta2-Adrenoceptor agonist modulates endothelin-1 receptors in human isolated bronchi.

Chronic exposure of human isolated bronchi to beta(2)-adrenergic agonists, especially fenoterol, potentiates smooth muscle contraction in response to endothelin-1 (ET-1), a peptide implicated in chronic inflammatory airway diseases. Our objective was to determine whether ET-1 receptors ETA and ETB are involved in fenoterol enhancement. Twenty-two human bronchi were sensitized to ET-1 by prolonged incubation with 0.1 microM fenoterol (15 h, 21 degrees C). Removing the epithelium after fenoterol incubation limited the maximal contraction (0.10+/-0.36 g without epithelium versus 1.18+/-0.22 with, n=8, P=0.04). After 15 h incubation, 14 and 8 paired rings were fixed, respectively, for immunolabeling of bronchial ETA and ETB receptors, and to determine the mRNA expression levels using real-time quantitative reverse transcription polymerase chain reaction. ETA and ETB receptor mRNA expressions were 1.27- +/- 0.14-fold (not significant) and 2.24- +/- 0.28-fold (P<0.01) higher, respectively, in fenoterol-treated bronchi than in paired controls. Fenoterol incubation significantly increased epithelial ETA and ETB receptor labeling intensity scores (P=0.001 and P=0.002, respectively, versus controls), and enhanced the diffuse localization of ETA receptors on the epithelial cells (P=0.002 versus controls), but did not change the ETB-receptor immunolabeling intensity on airway smooth muscle. We conclude that fenoterol-induced sensitization of human isolated bronchi involves epithelial ETA and ETB receptors, which suggests perturbation of the epithelial regulation of airway smooth muscle contraction in response to ET-1.

Adrenergic beta-Agonists↗
PubMed1993

Quantitative comparison of intracellular concentration and volume of Clara cell 10 KD protein in rat bronchi and bronchioles based on laser scanning confocal microscopy.

We used an antibody to rat Clara cell 10 KD secretory protein (CC10) to compare the abundance of CC10 in non-ciliated epithelium of bronchioles and bronchi by immunohistochemistry and laser scanning confocal microscopy (LSCM) in the reflectance mode. Three zones of reflectance intensity (high, medium, low), directly related to CC10 content, were used to distinguish subcellular compartments of differing densities. Two major compartments contained CC10: granules and endoplasmic reticulum. Bronchiolar cell granules had relatively even reflectance, a high CC10 concentration (0.92 mg/ml), and occupied 7.5% of the cell volume. Bronchial cell granules were bi-zonal, lower in CC10 concentration (0.83 mg/ml), and occupied less cell volume (2.3%). Low-reflecting endoplasmic reticulum occupied a greater cell volume in bronchioles than in bronchi (32.8% and 22.1%, respectively). An intermediate-density zone consisted of endoplasmic reticulum close to granules. CC10 abundance, expressed as ng stored per unit surface area of epithelial basal lamina, was more than three times greater in bronchioles than in proximal bronchi (1.50 ng/mm2 vs 0.42 ng/mm2). These data demonstrate that the process of CC10 secretion differs markedly in non-ciliated epithelium of bronchi and bronchioles. Identifiable mucous-goblet cells did not contain CC10. The LSCM provides a method for quantifying intracellular CC10 pools in intact lung cells and has the potential for quantifying other proteins in subcellular compartments.

Animals↗
PubMed1993

Important role of peptide leukotrienes (p-LTs) in the resting tonus of isolated human bronchi.

The quality of the resting tonus in isolated human bronchi was investigated using a peptide leukotriene (p-LT) antagonist, a 5-lipoxygenase inhibitor and others. (E)-2,2-Diethyl-3'-[2-[2-(4-isopropyl)-thiazoyl]ethenyl]succina nilic acid sodium salt (MCI-826), a newly synthesized compound that is a highly selective antagonist to LTD4 and LTE4, markedly relaxed the isolated human bronchi at low concentrations. A selective and competitive arachidonate 5-lipoxygenase inhibitor, 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA-861), also potently lowered the tonus. In addition, a large amount of spontaneously formed p-LTs was detected in the isolated human bronchial tissue as well as the lung parenchymal tissue. The isolated human bronchi responded to indomethacin treatment with contractions and the acceleration of p-LT formation. Atropine, an anticholinergic; mepyramine, an antihistaminic; and OKY-046, a thromboxane synthetase inhibitor, all showed no effect on the resting tonus. Taking into consideration the high responsiveness of the human airway smooth muscle to p-LTs and the present results, which were different from those on isolated guinea pig tracheas, it is strongly suggested that the spontaneously formed p-LTs largely participate in the resting tonus of the majority of isolated human bronchi.

Animals↗
PubMed2004

Nerve plexuses in the trachea and extrapulmonary bronchi of the rat.

Intrinsic nerve plexuses of the rat trachea and extrapulmonary bronchi were examined by immunohistochemistry. Three nerve plexuses--peritracheal and peribronchial, intramuscular, and submucosal--were found in the wall of the trachea and bronchi. Nerve cell bodies were located in the peritracheal and peribronchial nerve plexuses. They occurred singly or formed ganglia in the plexus, and regional differences in cell numbers were found in the cervical and thoracic portions of the trachea and in the extrapulmonary bronchia. In total, 83.5 +/- 28.3 ganglia (mean +/- SD, 57-131, n=5) and 749.8 +/- 221.1 nerve cell bodies (540-1,080, n=5) were found in the nerve plexus. The mean densities of ganglia were 0.31, 0.97 and 1.15/mm2, and the mean densities of the nerve cell bodies were 1.82, 9.26 and 11.54/mm2 in the cervical region, thoracic region of trachea, and extrapulmonary bronchi, respectively. Almost all nerve cell bodies in ganglia were positive for choline acetyltransferase and neuropeptide Y (NPY), and a few cells were positive for vasoactive intestinal peptide (VIP). In addition, in cholinergic nerves, a few nerve fibers in the smooth muscles were positive for substance P (SP), calcitonin gene-related peptide (CGRP), and VIP, and a moderate number of fibers were positive for NPY. Tyrosine hydroxylase-immunoreactive nerve fibers were observed around blood vessels and within nerve bundles in the tunica adventitia. In the epithelium, nerve fibers were positive for SP and CGRP. Our results indicate that postganglionic neurons form three layers of cholinergic plexuses in the rat trachea and extrapulmonary bronchi, and that all of these possess intrinsic and extrinsic peptidergic innervation.

Animals↗
PubMed1988

Pharmacologic responsiveness of rat parenchymal strips, bronchi, and bronchioles.

It has been inferred from previous studies that leukotrienes C4 and D4 preferentially exhibit their effects on peripheral airways. Thus we used LTC4 to examine the responsiveness of parenchymal strips, lung preparations often used as in vitro models of airway function, and to compare the responses with those observed in a preparation of isolated peripheral airways. In these studies, the effects of LTC4 on isolated bronchioles of the rat were compared to responses observed in parenchymal strips and primary intrapulmonary bronchi. Parenchymal strips contracted in response to increasing concentrations of LTC4 and to a single concentration of bethanechol. When the maximum responses were normalized to that induced by membrane depolarization, it was found that the parenchymal strip was more responsive to the leukotriene. Primary intrapulmonary bronchi similarly contracted in response to LTC4; however, the intrapulmonary bronchi were much more responsive to bethanechol than to the leukotriene. The bronchioles were not responsive to LTC4 but did contract in response to membrane depolarization and on exposure to bethanechol. When normalized, the responsiveness of the bronchiole to bethanechol was significantly greater than the responsiveness of the bronchi to this agonist. Thus contraction of the rat parenchymal strip to LTC4 cannot be attributed to the direct effects of this agonist on bronchiolar smooth muscle. We conclude that the bronchiole of the rat is not responsive to LTC4 and that the contractions observed in the parenchymal strip in response to this agonist must result from a mechanism other than direct action of LTC4 on peripheral airway smooth muscle.

Animals↗
PubMed1993

Cryopreservation of human bronchi.

Human bronchi have been investigated in vitro without or after storage at -196 degrees C in different media containing 1.8 M dimethyl sulfoxide and 0.1 M sucrose as cryoprotectants, dissolved in either fetal calf serum (FCS), Krebs-Henseleit solution (KH), or 50% FCS in KH as vehicles. As assessed by the post-thaw responses to both carbachol and histamine, optimal preservation of contractile responsiveness was obtained with bronchi that had been frozen in a medium containing KH solution as the vehicle. With each group of cryopreserved bronchi, maximal responses to relaxant agonists such as isoprenaline, papaverine, and the potassium channel activator bimakalim were attenuated by up to 50%, and the passive resting tension after maximal pharmacological relaxation was considerably higher than in the unfrozen tissues. The evidence suggests that, despite some reduction in elasticity, cryopreservation of human bronchi at -196 degrees C preserves both contractile and relaxant mechanisms and offers clear potential for storing human airway smooth muscle for subsequent pharmacological experiments.

Animals↗
PubMedDate not supplied

Histologic changes in donor bronchi may explain the reduced mucosal blood flow seen during acute lung allograft rejection.

We assessed the histologic changes in donor and recipient bronchi from 15 dogs that had received a lung transplant and related these changes to the severity of acute rejection seen in the parenchyma of these same lungs. Minimal rejection was associated with no abnormal change in either the donor or the recipient bronchi. In mild lung rejection, mononuclear cell cuffings were seen around bronchial arteries in donor bronchial adventitia, although few mononuclear cell infiltrates were seen in the submucosa. Moderate lung rejection was associated with more prominent mononuclear cell cuffings in the donor bronchial adventitia and mucosal infiltrates of mononuclear cells in the membranous portion. In cases of severe lung rejection, the mononuclear cell infiltrates were also apparent in the cartilaginous portion of the donor bronchial mucosa. Moreover, submucosal edema and detachment of bronchial epithelium were seen. These histologic changes were not observed in the recipient bronchi during acute rejection, nor were they seen in the donor and the recipient bronchi during lung infection without rejection. They might, therefore, reflect acute rejection in the donor bronchus. These results might provide the histologic support for our previous observation of decreased bronchial mucosal blood flow measured by the laser Doppler flowmeter in relation with the extent of acute lung rejection.

Acute Disease↗
PubMed1991

[Recent trial of bronchoplasty: reconstruction of air way in the vicinity to the segmental bronchi].

With modern techniques sleeve lobectomy is the safe method of surgery for lung diseases. The reports of reconstructive surgery of more peripheral bronchi are still a few. We experienced anastomosis at the vicinity to the segmental bronchi in 11 patients with 3 central early cancers, 2 synchronous double cancers, 1 adenoid cystic carcinoma, 1 pulmonary metastasis and 4 stage III lung cancers. Operative procedures were sometimes complicated and various. Wedge segmentectomy were performed in 4 cases, of whom one patient died from pneumonia after persistent pulmonary fistula. Sleeve resectin of the segmental bronchi were performed in 7 patients, of whom one patient died from anastmotic dehiscence due to empyema thoracis induced by MRSA, another died suddenly from pulmonary infarction one month after operation. Two causes of 3 hospital deaths could not be anticipated and there was no relation with bronchoplastic procedure. Reconstructive surgery in the peripheral bronchi should be indicated for patients with central early cancer, low grade malignancy of the lung and sometimes patients with hypolung function.

Aged↗
PubMed1990

[Thin-section computed tomography of the bronchi; 2. Right upper lobe and left upper division].

Thin (2mm) section contiguous computed tomographic (CT) scans were obtained through the bronchi of the right upper lobe and the left upper division in 30 patients. All segmental bronchi were identified. The right subsegmental bronchi were identified in 100%, and the left subsegmental bronchi in 97%. The type of the orifice of the right bronchus was trifurcated (53%), the extension of B1 was apicoanterior (50%), and the size of B2b was equal to B3a (63%). The extension of the left B3 was subapicoanterior (38%), and the size of B1+2c was equal to B3a (62%).

Adult↗
PubMed1986

Distribution of submucous gland in the human trachea, main and segmental bronchi: morphometric study.

A profile method of depicting the distribution of submucous gland in the human trachea and bronchi has recently been described from this laboratory. In that study the gland was assessed only in samples taken from the trachea and bronchi. The present study confirmed the validity of the sampling technique used by showing that the results obtained with it were representative of the amount of submucous gland as it varied throughout the whole length of the trachea and main bronchi in 1 case and around the trachea in a 2nd case. In addition the amount of gland in each of the 19 segmental bronchi of the 1st case was measured. This was found to be significantly less than the only previous measurements reported, probably because the effects of smoking in the latter were not taken into account. Nevertheless the present and previous measurements both show a previously unrecognised preponderance of gland on the right side at the segmental (generation 3/4) level, which could be related to the anatomy of the tracheobronchial tree.

Adult↗
PubMed1987

[Inter-organ neural communications in the innervation of bronchi and pulmonary circulation vessels].

By means of V.P. Vorobiov's preparation in complex of the thoracic cavity organs of persons at various age and sex in fetuses, sources of innervation of bronchi and vessels of the pulmonary circulation have been stated. They make the composition of the cardiac nerves getting off the superior, middle cervical, cervico-thoracic (stellate) and from 3 to 5 thoracic nodes of the sympathetic trunk, superior and inferior cardiac branches of the nervus vagus. Connection between the nerves of the bronchi and vessels of the pulmonary circulation with the cardiac and esophageal nerves and formation of interorganic nervous plexuses are demonstrated. Not always the diaphragmal nerve participates in the innervation of the bronchi and pulmonary vessels. In total preparations and flat sections, elective revealing of the nervous elements with Shiff reagent in M. G. Shubich and A. B. Khodos modification and Gomori thiocholine method, makes it possible to follow connections of the pulmonary veins nerves with the left atrium, intrapulmonary connection of the perivascular and peribronchial plexuses, as well as participation of nervous elements of the pulmonary trunk in innervation of the right ventricle walls. There are multiple vegetative communications participating in innervation of the bronchi and vessels of the pulmonary circulation. The relations of the pulmonary nerves with the nerves of other thoracic organs are very complex; this explains the nature of the repercussive reactions of the lungs after surgical interventions performed in the other organs of the thoracic cavity.

Animals↗
PubMedDate not supplied

[The quantitative characteristics of the fibroblastic series of cells in the tunica submucosa of the human bronchi].

Quantity of cells of fibroblastic cells in the wall of human bronchi was studied in age aspect. The quantity of these cells in tunica submucosa of the bronchi belongs to different generations, in juvenile age approaching the level of the adults. In senile age numeral density of cells is less than that in infancy. Changes of cell numbers in all the age groups studied are more expressed in large bronchi. Numerical density of the cells of fibroblastic series in tunica submucosa of bronchial walls correlates with their diameter. In sites of bronchi branching into further generations numeral density of cells of fibroblastic series increases, which is, probably, connected with mechanical impact of the air flow on bronchial walls in these regions.

Adolescent↗
PubMed1996

[Extirpation of bronchi: experimental study].

Sixteen dogs were divided to two groups: experimental group (11) and control group (5). In the experimenta group, the arterial blood PO2SaO2, CaO2 and bronchography which were compared between before and after operation were normal and the bronchi position shown by bronchography was not changed and the residual lung afte bronchi extirpation was still in an expansive status. In the control group, segmental resections were performed. Compared with the experimental group, the residual lung tissues after bronchi extirpation only had little wound refection and no ateledasis and expanded well. No destruction was observed in the neighbouring lung tissues. But in the control group, the heavy destruction, consolidation and emphysema were observed in the adjacent normal lung tissues. It is concluced that the extirpation of bronchi can eliminate the residual cavity early after operation and has less destruction and do not destruct the adjacent normal lung tissues.

Animals↗
PubMed1998

Clinical photodynamic therapy for superficial cancer in the oesophagus and the bronchi: 514 nm compared with 630 nm light irradiation after sensitization with Photofrin II.

Photodynamic therapy (PDT) for cancer in the oesophagus and bronchi with red (630 nm) light may occasionally lead to wall perforation and fistula. Therefore, we investigated the clinical use of a less penetrating wavelength (514 nm) for the curative treatment of nine superficial carcinomas in the oesophagus and bronchi after photosensitization with Photofrin II. Tumours without infiltration beyond the submucosa in the oesophagus and beyond the lamina propria in the bronchi were considered as superficial cancers. The outcome and complications were compared with those of 13 superficial cancers treated with PDT and 630 nm light. In addition, we evaluated histologically the extent of the long-term tissue damage and scarring following treatment of six oesophageal cancers with either green or red light. At first endoscopic control, 7-10 days after PDT, tissue necrosis simply matched the illuminated area, without evidence of selective tumour damage. Six of nine tumours treated with 514 nm light had a complete response compared with nine of 13 after 630 nm irradiation. No perforation or fistula occurred in either treatment group. However, severe chest pain and fever with or without pleural effusion, consistent with occult perforation, were observed in three patients after 630 nm illumination in the oesophagus. Histologically, fibrous scarring in the three distinct sites treated with green light was limited to the superficial layers of the oesophagus. After red light treatment, transmural fibrosis with marked thinning of the oesophageal wall was evident in two of the three specimens available for inspection. These results indicate that PDT with 514 nm light has the potential to cure superficial cancer in the oesophagus and bronchi with essentially the same probability of success as red light. In the oesophagus, green light prevents deep tissue damage, thus reducing the risk of perforation.

Aged↗
PubMed1996

[Study of silver binding nucleolar organizer regions (AgNORs) in proliferative lesions of bronchi, colon and thyroid--semiautomatic computer image analysis].

Silver-binding nucleolar organizer regions (AgNORs) were studied in the proliferative lesions and in normal tissue of bronchi, colon and thyroid gland. In the histopathological samples AgNORs were seen as blacks dots more or less scattered within nuclei. The investigated parameters included the number and area of AgNOR-dots, the number of AgNOR clusters, the ratio of AgNOR dot area to the nuclear area and the area of single AgNOR dots. The measurements were done with the help of semiautomatic computer image analysis. In thyroid the differences between proliferative lesions and also normal gland tissue were strongly marked in the number of clusters. Low values were typical for oxyphilic neoplasms and papillary carcinomas--in oxyphilic neoplasms single clusters within nuclei were seen. In bronchi and colon the differences between proliferative lesions and also normal tissue were strongly marked in the number and area of dots. High values were typical for squamous cell carcinomas or adenocarcinomas whereas low values were in small cell carcinomas. The ratio of dot area to nuclear area and the area of single dots were similar in various lesions and also in the normal tissue of thyroid, bronchi and colon. This study have shown that in the proliferative lesions of bronchi, colon and thyroid AgNOR values, particularly the number and area of AgNOR dots or the number of the AgNOR clusters show differences and are related with the type of tissue, type of lesion or their malignant character and are also related with the size of nuclei.

Animals↗
PubMed1994

Inhibition by cromakalim, pinacidil, terbutaline, theophylline and verapamil of non-cholinergic nerve-mediated contractions of guinea-pig isolated bronchi.

Contractions induced by electrical field stimulation of sensory non-cholinergic excitatory nerves in guinea-pig isolated bronchi are due to the release of substance P (SP) and related tachykinins. Release of such neuropeptides are thought to play a pathophysiological role in asthma. Two K+ channel openers cromakalim (pD2 = 6.45; Emax = 95%) and pinacidil (pD2 = 6.06; Emax = 87%) were shown to concentration-dependently inhibit non-cholinergic nerve-mediated contractions in guinea-pig bronchi in vitro. Cromakalim (pD2 = 6.27; Emax = 25%) and pinacidil (pD2 = 6.03; Emax = 25%) each had a much lower inhibitory efficacy against contractions induced by exogenously applied SP but the same potency as found against contractile responses to non-cholinergic neurostimulation. Also the beta 2-adrenoceptor agonist terbutaline (pD2 = 8.29; Emax = 83%), the xanthine derivative theophylline (pD2 = 4.19; Emax = 100%) and the Ca2+ blocker verapamil (pD2 = 5.55; Emax = 100%) suppressed responses to non-cholinergic neurostimulation. Terbutaline (pD2 = 6.32; Emax = 74%), theophylline (pD2 = 3.25; Emax = 71%) and verapamil (pD2 = 4.01; Emax = 100%) had a 10-100-fold lower inhibitory potency against SP-induced contractions but each drug showed about the same efficacy as found against nerve-mediated contractions. Glibenclamide (1 microM) reversed the inhibitory effects of cromakalim and pinacidil on neurally-mediated contractions but did not influence the effects of terbutaline, theophylline and verapamil. The results demonstrate that cromakalim, pinacidil, terbutaline, theophylline and verapamil inhibit non-cholinergic excitatory neurotransmission in guinea-pig bronchi and suggest that they act preferentially at a pre-junctional site.

Animals↗