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Lung Airways (lung + airway)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Alcohol Stimulates Ciliary Motility of Isolated Airway Axonemes Through a Nitric Oxide, Cyclase, and Cyclic Nucleotide-Dependent Kinase Mechanism

ALCOHOLISM, Issue 4 2009
Joseph H. Sisson
Background:, Lung mucociliary clearance provides the first line of defense from lung infections and is impaired in individuals who consume heavy amounts of alcohol. Previous studies have demonstrated that this alcohol-induced ciliary dysfunction occurs through impairment of nitric oxide (NO) and cyclic nucleotide-dependent kinase-signaling pathways in lung airway ciliated epithelial cells. Recent studies have established that all key elements of this alcohol-driven signaling pathway co-localize to the apical surface of the ciliated cells with the basal bodies. These findings led us to hypothesize that alcohol activates the cilia stimulation pathway at the organelle level. To test this hypothesis we performed experiments exposing isolated demembranated cilia (isolated axonemes) to alcohol and studied the effect of alcohol-stimulated ciliary motility on the pathways involved with isolated axoneme activation. Methods:, Isolated demembranated cilia were prepared from bovine trachea and activated with adenosine triphosphate. Ciliary beat frequency, NO production, adenylyl and guanylyl cyclase activities, cAMP- and cGMP-dependent kinase activities were measured following exposure to biologically relevant concentrations of alcohol. Results:, Alcohol rapidly stimulated axoneme beating 40% above baseline at very low concentrations of alcohol (1 to 10 mM). This activation was specific to ethanol, required the synthesis of NO, the activation of soluble adenylyl cyclase (sAC), and the activation of both cAMP- and cGMP-dependent kinases (PKA and PKG), all of which were present in the isolated organelle preparation. Conclusions:, Alcohol rapidly and sequentially activates the eNOS,NO,GC,cGMP,PKG and sAC,cAMP, PKA dual signaling pathways in isolated airway axonemes. These findings indicate a direct effect of alcohol on airway cilia organelle function and fully recapitulate the alcohol-driven activation of cilia known to exist in vivo and in intact lung ciliated cells in vitro following brief moderate alcohol exposure. Furthermore, these findings indicate that airway cilia are exquisitely sensitive to the effects of alcohol and substantiate a key role for alcohol in the alterations of mucociliary clearance associated with even low levels of alcohol intake. We speculate that this same axoneme-based alcohol activation pathway is down regulated following long-term high alcohol exposure and that the isolated axoneme preparation provides an excellent model for studying the mechanism of alcohol-mediated cilia dysfunction. [source]

Functional impairment of cytotoxic T cells in the lung airways following respiratory virus infections

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2006
Simone Vallbracht
Abstract We investigated the differentiation phenotype and function of virus-specific and non-specific CTL that were recruited to the lung parenchyma and the bronchoalveolar space after respiratory virus infections. Soon after virus elimination, we observed functional impairment of CTL isolated from the airways in their ability to produce IFN-, and TNF-, and to lyse target cells. Impaired cytotoxicity was due to a reduced content of granzyme B and a reduced ability to mobilize lytic granules. This impairment in effector functions (a) was largely restricted to CTL in the lung airways, (b) affected both CTL specific for the infecting virus as well as those that were recruited non-specifically to the inflamed lung, (c) was independent of contact between CTL and their specific viral antigen, (d) was not restricted to terminally differentiated CTL but also affected resting memory CTL and (e) could be elicited by both respiratory syncytial virus and influenza virus and thus seemed to be largely independent of the infecting virus. These observations suggest that functional impairment of antiviral T cells in the lung is not the consequence of a viral escape strategy. It may rather result from the particular milieu in the bronchoalveolar space and reflect a host mechanism to prevent excessive pulmonary inflammation. [source]

Stochastic Morphometric Model of the Balb/c Mouse Lung

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 10 2010
Pierre Madl
Abstract The laboratory mouse is often used as a human surrogate in aerosol inhalation studies. Morphometric data on the tracheobronchial geometry of three in situ lung casts of the Balb/c mouse lung produced by the Air Pollution Health Effects Laboratory were analyzed in terms of probability density functions and correlations among the different airway parameters. The results of this statistical analysis reveal significant differences in diameters and branching angles between major and minor progeny branching off from the same parent airway at a given airway bifurcation. Number of bronchial airways generations along a given path, expressed by the termination probability, branching angles, and daughter-to-parent diameter ratios indicate that the location of an airway with defined linear airway dimensions within the lung is more appropriately identified by its diameter (or its parent diameter) than by an assigned generation number. We, therefore, recommend classifying the mouse lung airways by their diameters and not by generation numbers, consistent with our previous analysis of the rather monopodial structure of the rat lung (Koblinger et al., J Aerosol Med 1995;8:7,19; Koblinger and Hofmann, J Aerosol Med 1995;8:21,32). Because of lack of corresponding information on respiratory airways, a partly stochastic symmetric acinar airway model was attached to the tracheobronchial model, in which the number of acinar airways along a given path was randomly selected from a measured acinar volume distribution. The computed distributions of the geometric airway parameters and their correlations will be used for random pathway selection of inhaled particles in subsequent Monte Carlo deposition calculations. Anat Rec 293:1766,1786, 2010. © 2010 Wiley-Liss, Inc. [source]