The T cell-specific CXC chemokines IP-10, Mig, and I-TAC are expressed by activated human bronchial epithelial cells.
(25/4704)
Recruitment of activated T cells to mucosal surfaces, such as the airway epithelium, is important in host defense and for the development of inflammatory diseases at these sites. We therefore asked whether the CXC chemokines IFN-induced protein of 10 kDa (IP-10), monokine induced by IFN-gamma (Mig), and IFN-inducible T-cell alpha-chemoattractant (I-TAC), which specifically chemoattract activated T cells by signaling through the chemokine receptor CXCR3, were inducible in respiratory epithelial cells. The effects of proinflammatory cytokines, including IFN-gamma (Th1-type cytokine), Th2-type cytokines (IL-4, IL-10, and IL-13), and dexamethasone were studied in normal human bronchial epithelial cells (NHBEC) and in two human respiratory epithelial cell lines, A549 and BEAS-2B. We found that IFN-gamma, but not TNF-alpha or IL-1 beta, strongly induced IP-10, Mig, and I-TAC mRNA accumulation mainly in NHBEC and that TNF-alpha and IL-1 beta synergized with IFN-gamma induction in all three cell types. High levels of IP-10 protein (> 800 ng/ml) were detected in supernatants of IFN-gamma/TNF-alpha-stimulated NHBEC. Neither dexamethasone nor Th2 cytokines modulated IP-10, Mig, or I-TAC expression. Since IFN-gamma is up-regulated in tuberculosis (TB), using in situ hybridization we studied the expression of IP-10 in the airways of TB patients and found that IP-10 mRNA was expressed in the bronchial epithelium. In addition, IP-10-positive cells obtained by bronchoalveolar lavage were significantly increased in TB patients compared with normal controls. These results show that activated bronchial epithelium is an important source of IP-10, Mig, and I-TAC, which may, in pulmonary diseases such as TB (in which IFN-gamma is highly expressed) play an important role in the recruitment of activated T cells. (+info)
Site of functional bronchopulmonary anastomoses in sheep.
(26/4704)
The location of bronchopulmonary anastomoses has long been a topic of discussion, and pre-, post-, and capillary sites have all been demonstrated in postmortem examinations. However, there have been few studies that have provided insight into the patency and function of these anastomoses in the intact lung. To identify these functional sites where the bronchial circulation anastomoses with the pulmonary circulation, we studied sheep lungs in situ serial sectioned with high-resolution computed tomography (CT). Differences in radiodensities of blood, air, and nonionic contrast medium were used to differentiate and localize airways and vessels and to identify the effluent from the bronchial circulation. After an initial series of scans to identify the pulmonary arteries and veins adjacent to airways 2-12 mm in diameter, contrast material was infused into the bronchial artery. In three sheep, the major accumulation of contrast medium was found in pulmonary veins. In one of the sheep, a comparable number of pulmonary arteries and veins contained contrast medium. Serial histologic sections were able to identify small bronchial venules lying within subepithelial bronchial folds that drain directly into pulmonary veins. These results using serial CT and histologic images suggest that drainage from the intraparenchymal bronchial vasculature is predominantly into postcapillary pulmonary vessels. (+info)
Up-regulation of E-cadherin by an anti-epidermal growth factor receptor monoclonal antibody in lung cancer cell lines.
(27/4704)
Many human epithelial carcinomas are characterized by the overexpression and constitutive activation of the epidermal growth factor receptor (EGF-R) via an autocrine signaling loop. We have investigated the effects of a ligand-blocking monoclonal antibody (mAb) against the EGF-R LA1 on selected parameters of human lung cancer cell lines (H322 and H661) and normal human bronchial epithelial (NHBE) cells. Using Western blot analysis, we show that H322 and NHBE cell lines express comparable levels of EGF-R/p170erbB-1. The LA1 mAb against EGF-R inhibits growth, induces differentiation to a more epithelial phenotype, reduces the constitutive activation of EGF-R, and upregulates epithelial cadherin glycoprotein expression in H322 and NHBE cells. In contrast, LA1 had no effect on either growth, differentiation, receptor tyrosine phosphorylation, or the expression of adhesion molecules in H661 cells, which is consistent with our finding that this cell line does not express detectable levels of EGF-R. These studies demonstrate that a blocking anti-EGF-R mAb can regulate proliferation, differentiation, and the expression of cell adhesion molecules in human bronchial epithelial cells. Our findings suggest possible therapeutic avenues for the treatment of invasive carcinomas via the blockade of EGF-R with antibodies. (+info)
Nitrite reductase from Pseudomonas aeruginosa released by antimicrobial agents and complement induces interleukin-8 production in bronchial epithelial cells.
(28/4704)
We have recently reported that nitrite reductase, a bifunctional enzyme located in the periplasmic space of Pseudomonas aeruginosa, could induce interleukin-8 (IL-8) generation in a variety of respiratory cells, including bronchial epithelial cells (K. Oishi et al. Infect. Immun. 65:2648-2655, 1997). In this report, we examined the mode of nitrite reductase (PNR) release from a serum-sensitive strain of live P. aeruginosa cells during in vitro treatment with four different antimicrobial agents or human complement. Bacterial killing of P. aeruginosa by antimicrobial agents induced PNR release and mediated IL-8 production in human bronchial epithelial (BET-1A) cells. Among these agents, imipenem demonstrated rapid killing of P. aeruginosa as well as rapid release of PNR and resulted in the highest IL-8 production. Complement-mediated killing of P. aeruginosa was also associated with PNR release and enhanced IL-8 production. The immunoprecipitates of the aliquots of bacterial culture containing imipenem or complement with anti-PNR immunoglobulin G (IgG) induced twofold-higher IL-8 production than did the immunoprecipitates of the aliquots of bacterial culture with a control IgG. These pieces of evidence confirmed that PNR released in the aliquots of bacterial culture was responsible for IL-8 production in the BET-1A cells. Furthermore, the culture supernatants of the BET-1A cells stimulated with aliquots of bacterial culture containing antimicrobial agents or complement similarly mediated neutrophil migration in vitro. These data support the possibility that a potent inducer of IL-8, PNR, could be released from P. aeruginosa after exposure to antimicrobial agents or complement and contributes to neutrophil migration in the airways during bronchopulmonary infections with P. aeruginosa. (+info)
An account of the longitudinal mucosal corrugations of the human tracheo-bronchial tree, with observations on those of some animals.
(29/4704)
A description is given of the distribution of the longitudinal mucosal corrugations in the human tracheo-bronchial tree. It has been shown that they are made up of elastic tissue in a collagen matrix, and that the elastic fibres continue into the smallest bronchioles beyond where the corrugations are no longer visible. An examination has also been made of the tracheo-bronchial trees of the hen, rat, raccoon, pig, sheep, llama and tiger. Corrugations are present in all these animals, except the hen and the raccoon, and they have been compared and contrasted with the condition in Man. The functional significance of these corrugations remains unknown, but, they could be important in equalizing tension in the tracheo-bronchial tree during inspiration, as well as in providing elastic recoil during expiration. (+info)
Aspirated foreign bodies in the tracheobronchial tree: report of 250 cases.
(30/4704)
During the last 14 years, 250 patients with aspirated foreign bodies in the tracheobronchial tree were admitted to Kuwait Chest Diseases Hospital. Ninety-six per cent of the cases were under 10 years of age and 38% gave a clear history of foreign body inhalation. The rest were diagnosed either clinically, from the chest radiograph findings or because of unexplained pulmonary symptoms. In 247 cases, bronchoscopy under general anaesthesia was successful in removing the foreign bodies. In only three cases was bronchotomy needed. Seventy per cent of the foreign bodies were melon seeds. Asphyxia and cardiac arrest occurred in four cases during bronchoscopy but the patients were successfully resuscitated. In 10 cases a tracheostomy was done before bronchoscopy and the removal of the foreign body, while in five it was needed after bronchoscopy. Fifteen patients developed late complications such as recurrent pneumonia or atelectasis of the lung. Early diagnosis and adequate treatment are essential to prevent pulmonary and cardiac complications and to avoid radical lung surgery. (+info)
Pattern of total and regional lung function in subjects with bronchoconstriction induced by 15-me PGF2 alpha.
(31/4704)
Closing volume (single breath nitrogen test), regional ventilation and perfusion (using intravenous xenon-133), and total lung function (TLC, VC, and FEV) were measured before and after intramuscular administration of 250 mug 15-methyl prostaglandin F2alpha (15-me PGF2alpha) in 10 healthy women. The cardiac output was measured with the Minnesota impedance cardiograph model 304A and the transthoracic impedance was used as an expression of the thoracic fluid volume. The slope of the alveolar plateau on the closing volume tracing showed a 271% increase 20 minutes after the prostaglandin administration, at which time the closing volume per cent (CV%) had decreased (P less than 0-01) and the closing capacity (CC%) had increased (P less than 0-05). Vital capacity (VC) decreased (P less than 0-01), residual volume (RV) increased (P less than 0-01), and the total lung capacity (TLC) remained unchanged. The maximal decrease (9%) in FEV1 was seen after 20 minutes. All these measurements except the slope of the alveolar plateau returned to control levels after 60 minutes. The redistribution of regional ventilation was more pronounced than that of the regional pulmonary blood flow. No change was observed in cardiac output and transthoracic impedance. None of the patients experienced any dyspnoea. Our results are consistent with a more pronounced effect of prostaglandin F2alpha on the small airways (the alveolar plateau) than on the larger airways (FEV1). In cases where an increase in the slope of the alveolar plateau is observed, the closing volume per cent should not be used as a measurement of the lung disease. It is concluded that the single breath nitrogen test (N2 closing volume) is more sensitive than the conventional tests. (+info)
Secretory cells of the peripheral pulmonary epithelium as targets for toxic agents.
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The extracellular lining of the pulmonary peripheral airways is of vital importance to the lung. In this report, some aspects of the pulmonary extracellular lining and the epithelial cells believed to be responsible for its formation and secretion have been briefly reviewed. The influence of a number of toxic agents on the extracellular lining either directly or via those cells involved in its formation indicates that the extracellular lining may be important in understanding numerous toxic agent interactions with the lung. (+info)