Lung Responses (lung + response)

Distribution by Scientific Domains


Selected Abstracts


Effects of oral alpha-tocopherol on lung response in rat model of allergic asthma

RESPIROLOGY, Issue 4 2006
Jana SUCHANKOVA
Objective and background: Asthma is a chronic inflammatory disease in which an oxidant/antioxidant imbalance plays an important role. d -alpha-tocopherol (biologically the most active form of vitamin E) has redox properties and by scavenging the free radicals can act as an antioxidant. The aim of this study was to examine the effects of orally administered alpha-tocopherol in a rat model of allergic asthma. Methodology: Actively sensitized rats (OA) were treated with alpha-tocopherol (400 mg/kg/day for 10 days) or vehicle; 1 h after the last dose, they were challenged with antigen aerosol. The antigen-induced airway hyperresponsiveness to direct bronchoconstrictor (serotonin), the inflammatory cell infiltrate and histological changes were determined 1 or 24 h after the antigen challenge. Results: Alpha-tocopherol pretreatment was not significantly effective at reducing the studied parameters when compared with controls, even though there was a tendency to a reduction in bronchial responsiveness and in eosinophil and neutrophil infiltration. Conclusion: Alpha-tocopherol when administered in the chosen study design in an animal model of asthma had no major effect on airway inflammation. The effect of antioxidants deserves further evaluation. [source]


Sex differences in response to steroids in preterm sheep lungs are not explained by glucocorticoid receptor number or binding affinity,

PEDIATRIC PULMONOLOGY, Issue 1 2001
Jana Kovar BScHons
Abstract We recently reported that prenatal glucocorticoid therapy is less effective at promoting an improvement in lung function in male than in female sheep. This observation, and the higher incidence of respiratory distress syndrome in human males, suggests that the male fetal lung may be less responsive to glucocorticoids than is the female fetal lung. Since glucocorticoids are known to exert their effects via specific cytoplasmic glucocorticoid receptors (GR), we hypothesized that there may be sexual dimorphism in either the number or binding affinity of lung GR. To test the hypothesis, binding of dexamethasone (a synthetic glucocorticoid, 0.5,40 nM) by cytosolic fractions of male (n,=,16) and female (n,=,16) fetal sheep lung was measured at 125 days gestation (term,=,148 days). Scatchard analysis of dexamethasone binding showed that the total number of GR (Bmax) did not significantly differ between male (346,±,42 fmol/mg protein) and female (277,±,23 fmol/mg protein) fetuses. The measured binding affinity (Kd) in male fetal lungs (6.85,±,0.43 nM) was not significantly different from that in females (8.46,±,1.02 nM). In conclusion, this study suggests that sex differences in fetal sheep lung responses to glucocorticoid therapy are not due to differences in the number or binding affinity of lung GR. Pediatr Pulmonol. 2001; 32:8,13. © 2001 Wiley-Liss, Inc. [source]


Antithetical effect of tumor necrosis factor-,gene polymorphism on coal workers' pneumoconiosis (CWP),

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 1 2005
Xin-Tao Wang MD
Abstract Background Inter-individual variation in the severity of pneumoconiosis has been described, even with the same environmental exposure. We hypothesized that TNF-, promoter polymorphisms associate with lung responses to environmental exposure in coal worker's pneumoconiosis (CWP) patients. Methods We examined polymorphisms at ,238, ,308, and ,376 in 124 patients with CWP who had similar dust exposure history and in 122 non-exposed controls. CWP patients were divided into two groups: (1) nodular CWP (n,=,84); (2) progressive massive fibrosis (PMF) (n,=,44). Results The ,308 A allele frequency was higher in patients with CWP compared to controls (6.35% and 2.05%, P,<,0.01). It was also higher in patients with nodular CWP compared to PMF (P,<,0.05). Logistic regression analysis revealed that patients with the ,308 A allele were 3.8 times (P,=,0.036) and those with smoking habit were 2.3 times (P,<,0.002) more likely to have nodular CWP than PMF. Conclusion TNF-,-308 A allele might interact with smoking to enhance susceptibility to nodular CWP. Am. J. Ind. Med. 48:24,29, 2005. © 2005 Wiley-Liss, Inc. [source]


Local lung responses following local lung challenge with recombinant lungworm antigen in systemically sensitized sheep

CLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2001
D. D. S. Collie
Background Chronic mast cell-mediated inflammation may contribute significantly towards the extensive tissue remodelling that is a feature of lungworm infection in ruminants. Understanding the factors that control tissue remodelling is a necessary step toward effective management and treatment of conditions that feature such pathology. Objective We sought to define in a novel ovine model system, the cellular, immune and mast cell phenotypic events that occur following local lung challenge with a recombinant protein antigen, DvA-1, derived from the ruminant lungworm nematode, Dictyocaulus viviparus. Methods Two spatially disparate lung segments in systemically sensitized sheep were challenged on three occasions with DvA-1 (3xDVA) and two further segments were challenged with saline (3xSAL). Two months after the third challenge, one of the two segments previously repeatedly challenged with DvA-1 was challenged again with DvA-1 (3xDVA:DVA) whilst the other was challenged with saline (3xDVA:SAL). A similar protocol was followed with the saline challenged segments (3xSAL:SAL and 3xSAL:DVA). Bronchoalveolar lavage fluid (BALF) (n = 16) and tissue (n = 3) were collected after the last challenge. Results Cellular changes 24 h after the fourth challenge were characterized by an increase in the absolute numbers of neutrophils and eosinophils in BALF from 3xDVA:DVA and 3xSAL:DVA segments. Local antibody production was implied through increased levels of antibody in both 3xDVA:DVA and 3xDVA:SAL segments, with the latter being unaffected by inflammation. Levels of active transforming growth factor beta-1 (TGF-,1) were significantly increased in 3xDVA:SAL segments and a trend towards an increase was apparent in 3xDVA:DVA segments. Total TGF-,1 levels were significantly correlated with eosinophil counts in all except the 3xDVA:SAL segments. Such changes in the bronchoalveolar space were complemented by increased ratios of sheep mast cell proteinase-1 expressing cells and tryptase expressing cells, to toluidine blue positive cells in airways from 3xDVA:DVA segments. Conclusion Mast cell phenotypic events occurring as a consequence of antigen challenge were limited to segments in which changes in BALF were characterized by neutrophil influx and increased local antibody production. [source]


Ethanol Exposure Impairs LPS-Induced Pulmonary LIX Expression: Alveolar Epithelial Cell Dysfunction as a Consequence of Acute Intoxication

ALCOHOLISM, Issue 2 2009
James E. Walker Jr
Background:, Alcohol intoxication impairs innate immune responses to bacterial pneumonia, including neutrophil influx. Lipopolysaccharide (LPS)-induced chemokine (LIX or CXCL5) is a recently described chemokine produced by type-II alveolar epithelial (AE2) cells which facilitates neutrophil recruitment. The effect of acute alcohol intoxication on AE2 cell expression of LIX is unknown. Methods:, C57BL/6 mice were given an intraperitoneal (i.p.) injection of ethanol (4 g/kg) or saline 30 minutes prior to intratracheal (i.t.) injection with 10 ,g Escherichia coli LPS. In vitro stimulation of primary AE2 cells or murine AE2 cell line MLE-12 was performed with LPS and tumor necrosis factor-alpha (TNF-,). Results:, LIX protein is readily detectable in the lung but not in plasma following LPS administration, demonstrating "compartmentalization" of this chemokine during pulmonary challenge. In contrast to the CXC chemokines keratinocyte-derived chemokine and macrophage inflammatory protein-2, which are abundantly expressed in both lung tissue and alveolar macrophages, LIX expression is largely confined to the lung parenchyma. Compared to controls, intoxicated animals show a decrease in LIX and neutrophil number in bronchoalveolar lavage fluid following LPS challenge. Ethanol inhibits LIX at the transcriptional level. In vitro studies show that LPS and TNF-, are synergistic in inducing LIX by either primary AE2 or MLE-12 cells. Acute ethanol exposure potently and dose-dependently inhibits LIX expression by AE2 cells. Activation of nuclear factor-,B is critical to LIX expression in MLE-12 cells, and acute ethanol treatment interferes with early activation of this pathway as evidenced by impairing phosphorylation of p65 (RelA). Inhibition of p38 mitogen-activated protein kinase signaling, but not ERK1/2 activity, in MLE-12 cells by acute alcohol is likely an important cause of decreased LIX expression during challenge. Conclusions:, These data demonstrate direct suppression of AE2 cell innate immune function by ethanol and add to our understanding of the mechanisms by which acute intoxication impairs the lung's response to microbial challenge. [source]