American journal of respiratory cell and molecular biology
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Am. J. Respir. Cell Mol. Biol. · Oct 2000
Differential gene expression in the initiation and progression of nickel-induced acute lung injury.
Acute lung injury, an often fatal condition, can result from a wide range of insults leading to a complex series of biologic responses. Despite extensive research, questions remain about the interplay of the factors involved and their role in acute lung injury. We proposed that assessing the temporal and functional relationships of differentially expressed genes after pulmonary insult would reveal novel interactions in the progression of acute lung injury. ⋯ The overall pattern of gene expression was consistent with oxidative stress, hypoxia, cell proliferation, and extracellular matrix repair, followed by a marked decrease in pulmonary surfactant proteins. Also, expressed sequence tags (ESTs), with nominal homology to known genes, displayed similar expression patterns to those of known genes, suggesting possible roles for these ESTs in the pulmonary response to injury. Thus, this analysis of the progression and response to acute lung injury revealed novel gene expression patterns.
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Am. J. Respir. Cell Mol. Biol. · Oct 2000
Clinical TrialEffect of cigarette smoke on the permeability and IL-1beta and sICAM-1 release from cultured human bronchial epithelial cells of never-smokers, smokers, and patients with chronic obstructive pulmonary disease.
Although cigarette smoking is of paramount importance in the development of chronic obstructive pulmonary disease (COPD), only a small proportion of smokers develop the disease. We tested the hypothesis that the response of the bronchial epithelium to cigarette smoke (CS) differs in patients with COPD. Such a difference might explain in part why only some cigarette smokers develop the disease. ⋯ Exposure to CS significantly decreased the concentration of intracellular GSH in all cultures. However, the fall in intracellular GSH was significantly greater in cells from patients with COPD (mean 72.9% decrease) than in cells from never-smokers (mean 61.4% decrease; P = 0.048) or smokers with normal pulmonary function (mean 43.9% decrease; P = 0.02). These results suggest that whereas smokers with or without COPD demonstrate increased levels of GSH within bronchial epithelial cell cultures, those with COPD have a greater susceptibility to the effects of CS in reducing GSH levels and causing increased permeability and release of proinflammatory mediators such as IL-1beta and sICAM-1.
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Am. J. Respir. Cell Mol. Biol. · Apr 2000
Comparative StudyPartial liquid ventilation with perfluorocarbon in acute lung injury: light and transmission electron microscopy studies.
Liquid ventilation using perfluorocarbon has been shown to improve gas exchange in animal models of acute lung injury as well as in children with acute respiratory distress syndrome. This study was designed to define structural features of lung injury following partial liquid ventilation (PLV) using light and transmission electron microscopy in a rabbit model of acute respiratory distress. Animals were treated with either conventional mechanical ventilation (CMV-gas) (n = 6) or PLV (n = 5) for 4 h after the induction of acute lung injury with saline lavage. ⋯ Fluorescence microscopy analysis shows fewer type II alveolar epithelial cells in the CMV group and brighter type II cells in the PLV group. Transmission electron microscopy studies show more alveolar wall damage in the CMV group, with type II cells detached from their basement membrane with fewer surfactant-containing lamellar bodies. We conclude that quantitative histologic analysis shows less lung damage and inflammation when perfluorocarbon is combined with CMV in the management of acute respiratory distress syndrome.
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Am. J. Respir. Cell Mol. Biol. · Sep 1999
Mechanisms and regulation of polymorphonuclear leukocyte and eosinophil adherence to human airway epithelial cells.
Polymorphonuclear leukocytes (PMN) and eosinophils (Eos) are important cellular participants in a variety of acute and chronic inflammatory reactions in the airway. Histologic evidence has implicated direct interactions between these two subsets of leukocytes and airway epithelial cells during inflammation. A comprehensive characterization and comparison of physiologic stimuli and adhesion molecule involvement in granulocyte-epithelial-cell interactions done with nontransformed human airway epithelial cells has not been reported. ⋯ Adhesion of both Eos and PMN was inhibited by treatment of HBECs with blocking antibodies to ICAM-1. Differential utilization of beta(1) and beta(2) integrins by Eos, depending on the activation state of the epithelium, is a novel finding and may affect activation and/or recruitment of Eos in airway tissue. Mechanisms of adhesion of HBECs to Eos and PMN, as evidenced by the different responsiveness of the two latter types of cells to IL-8 and IL-5, may account for a prevalence of Eos over PMN in certain airway diseases.
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Am. J. Respir. Cell Mol. Biol. · Sep 1999
Normal surfactant pool sizes and inhibition-resistant surfactant from mice that overexpress surfactant protein A.
Pulmonary surfactant protein-A (SP-A) has been reported to regulate the uptake and secretion of surfactant by alveolar type II cells, to stabilize large surfactant aggregates including tubular myelin, and to protect the surface activity of surfactant from protein inhibitors. In this study we investigated the consequences of overexpression of SP-A on pulmonary homeostasis and surfactant function in transgenic mice. The human SP-C promoter was used to direct synthesis of rat surfactant protein A (rSP-A) in alveolar type II cells and nonciliated bronchiolar cells of the distal respiratory epithelium. ⋯ There were no differences between the transgene-positive and -negative mice in the tissue or alveolar pool sizes of saturated phosphatidylcholine or in the large-aggregate composition of alveolar surfactant. The surface activity of surfactant isolated from the rSP-A mice was similar to that of the controls, but in the presence of protein inhibitors, the surface tension-reducing properties of the rSP-A surfactant were better preserved (P < 0.05). We conclude that overexpression of SP-A does not affect resting surfactant phospholipid levels, but that it enhances the resistance of surfactant to protein inhibition.