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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lung injury caused by breathing enriched oxygen continues to be a major problem in clinical medicine. Experimentally, hyperoxic lung injury is characterized by pulmonary edema and associated neutrophil accumulation. Although extensively investigated, the mechanisms for neutrophil accumulation and the role of this accumulation in hyperoxic lung injury remain controversial. Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule that when increased on endothelium by inflammatory cytokines leads to increased adhesion of neutrophils to the inflamed endothelium and transendothelial migration. The purpose of this study was to examine the role of inflammation in hyperoxia-induced lung injury by investigating ICAM-1 expression in the lungs of mice exposed to > 95% oxygen continuously. Lung tissue from mice exposed to > 95% oxygen was analyzed for ICAM-1 mRNA by slot blot analysis and for ICAM-1 protein expression. We also examined lungs from mice exposed to hyperoxia for up to 96 h by light microscopy to correlate pulmonary inflammation with ICAM-1 expression. We found that mRNA for ICAM-1 increased 56% over baseline after 48 h of exposure to hyperoxia, that ICAM-1 protein increased by more than 5-fold over baseline after 96 h of exposure to hyperoxia, and that lung inflammation and injury were not evident until 96 h of exposure. Our data demonstrate that exposure to hyperoxia causes an increase in ICAM-1 gene transcription and/or mRNA stability in mouse lungs, and that this increase is followed by an increase in ICAM-1 protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increases in lung tissue expression of intercellular adhesion molecule-1 are associated with hyperoxic lung injury and inflammation in mice. 810 35

Cell-to-cell communication is often disrupted when tissue damage occurs, triggering new signals to cope with the injury. The expression of intercellular adhesion molecule (ICAM-1), a protein involved in the migration, binding, and activation of leukocytes, is markedly increased in mouse lungs damaged by acute hyperoxic exposure. Type I alveolar epithelial cells are sensitive to hyperoxic lung injury, and must be removed from the air spaces following their destruction. In contrast, type II pneumocytes are relatively resistant to hyperoxia and may have a role in the removal process. Two reports demonstrate increased ICAM-1 in alveoli after hyperoxia (Welty et al., 1993, AJRCMB 9:393-400; and Kang et al., 1993, AJRCMB 9:350-355), but the cellular site(s) of ICAM-1 synthesis were not determined. We hypothesized that during in vivo exposure to 100% oxygen (O2), type II pneumocytes synthesize and secrete ICAM-1, an important step in attracting inflammatory cells to the site of injury. Adult mice were exposed to 100% O2 for up to 72 h. To determine whether type II cells express ICAM-1, tissue sections were studied by electron microscopy single-label in situ hybridization or light microscopy dual-label in situ hybridization, using radiolabeled and nonradiolabeled probes. In the lungs of unexposed animals, ICAM-1 mRNA was detected in many cells-including type I pneumocytes-but not in type II cells. After hyperoxia, ICAM-1 transcripts were detected in bona fide, surfactant protein C mRNA-containing, type II alveolar epithelial cells. This observation suggests that type II cells play an important and previously unrecognized role in pulmonary inflammation from O2 toxicity and emphasizes the importance of type II pneumocytes in alveolar repair after injury.
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PMID:In vivo expression of intercellular adhesion molecule 1 in type II pneumocytes during hyperoxia. 867 24

The pulmonary damage caused by prolonged exposure to high oxygen concentrations is accompanied by lung inflammation, which may contribute to the expression of hyperoxic lung injury. In turn, adhesion molecules are crucial for initiating inflammatory responses. The goal of the present study was to investigate the association of contents of soluble adhesion molecules in plasma or alveolar fluids of hyperoxic rats with lung expression of adhesion molecules, lung inflammation and lung injury. We exposed adult Sprague-Dawley rats to > 95% oxygen for up to 60 h and measured the contents of intercellular adhesion molecule-I (ICAM-I) and E-Selectin in plasma and lung tissue expression of the same molecules, and we assessed lung myeloperoxidase (MPO) activties and lung water contents as indices of lung inflammation and injury, respectively. We also assessed ICAM-I content in lavage samples, because ICAM-I may be shed from the alveolar epithelium. Lung water was elevated at 60 h of hyperoxia-exposure, and this effect was preceded by increases in lung MPO activities. Lung ICAM-I expression was more than doubled at 48 h, although soluble ICAM-I contents were not elevated in plasma or lavage. Soluble E-Selectin was increased by more than 50% at 24 h of hyperoxia-exposure, while lung expressions of E-Selectin were not increased until 48 h. The sequence of the events observed in the present studies suggests that E-Selectin contributes to lung inflammation in hyperoxia and the acceleration of lung injury immediately following the inflammatory response suggests a pivotal role for inflammation in this injury.
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PMID:Increased soluble E-Selectin is associated with lung inflammation, and lung injury in hyperoxia-exposed rats. 891 24

Exposure to high concentrations of oxygen is known to induce changes in lung function through effects on several pulmonary cell types, including alveolar macrophages (AM). In this study, we studied the in vitro effects of hyperoxia on the release of proinflammatory cytokines and the expression of surface receptors in AM obtained from cynomolgus monkeys by bronchoalveolar lavage under general anesthesia. AM were exposed for 24 h to moderate (50% O(2)) or severe (95% O&sub2) hyperoxia in the absence or presence of LPS, and the release of IL-1beta, IL-6, and TNF-alpha was measured in culture supernatants by ELISA. In addition, the expression of the surface molecules HLA-DR, CD14, and CD11b was assessed by flow cytometry. Exposure to 95% O2 activated resting AM to produce significantly increased amounts of IL-1beta and IL-6. Moreover, hyperoxia amplified the release of TNF-alpha by LPS-stimulated AM in an oxygen tension-dependent manner. Finally, exposure to 95% O2 upregulated the expression of the adhesion molecule CD11b on AM, whereas the expression of HLA-DR and CD14 was not affected. These findings support the view that hyperoxia-induced activation of AM may represent an initial event in the proinflammatory sequence caused by hyperoxia.
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PMID:Hyperoxia induces upregulation of CD11b and amplifies LPS-induced TNF-alpha release by alveolar macrophages. 911 Sep 20

To investigate the pathogenesis of pulmonary oxygen toxicity, we examined the effect of hyperoxia on adhesion molecule expression in cultured human pulmonary artery endothelial cells (HPAEC) and human umbilical vein endothelial cells (HUVEC). Endothelial cell monolayers were exposed to either hyperoxic (90% O(2)-5% CO(2)) or normoxic (21% O(2)-5% CO(2)) conditions for various periods. The level of intercellular adhesion molecule (ICAM)-1 expression had increased in hyperoxia-exposed HPAEC and HUVEC at 48 h (194 +/- 38 and 233 +/- 56%, respectively; P < 0.001) and at 72 h (200 +/- 43 and 223 +/- 52%, respectively; P < 0.001) compared with normoxic conditions. These hyperoxia-induced ICAM-1 expressions were dose dependently attenuated by a protein kinase C inhibitor (H-7). In contrast, the levels of P-selectin and E-selectin expression in HPAEC and HUVEC were unchanged. The levels of ICAM-1 mRNA and the numbers of adherent neutrophils were increased in HPAEC and HUVEC at 48 and 72 h of hyperoxia. On the other hand, hyperoxia caused neutrophil H(2)O(2) production without affecting the level of CD11/CD18 expression. These results suggest that increased ICAM-1 expression in endothelial cells plays an important role in neutrophil accumulation during hyperoxia.
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PMID:Effect of hyperoxia on adhesion molecule expression in human endothelial cells and neutrophils. 912 98

Leukocyte infiltration plays a major role in ischemia-associated organ dysfunction and damage. A crucial step for extravasation of white blood cells is binding of leukocyte beta-integrins to endothelial adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). To test for direct effects of oxygen on this process we studied ICAM-1 and VCAM-1 expression in human dermal microvascular and umbilical vein endothelial cells (EC) exposed to different oxygen tensions in the absence or presence of tumor necrosis factor-alpha (TNF-alpha). Hypoxia (95% N2-5% CO2) resulted in a downregulation of basal but not TNF-alpha-induced expression of ICAM-1 and VCAM-1. Subsequent rises in oxygen (21, 40, or 95% O2) led to marked increase of ICAM-1 and VCAM-1 cell surface and mRNA expression in both EC types, which after 16 h amounted to about one-third to one-half of maximal TNF-alpha-induced expression. This increase was greatest after 0.5-h hypoxia and was blunted with prolonged hypoxic preincubation. Exposure of cells preincubated under "normoxic" (21% O2) conditions to hyperoxia (40 or 95% O2) also enhanced expression of both adhesion molecules, but the increase was lower than in cells preexposed to hypoxia. The nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) enhanced ICAM-1 and VCAM-1 expression under basal and hypoxic conditions, but in the presence of L-NAME, levels in reoxygenated cells were not higher than basal levels. Moreover, the oxygen-induced rise could be mimicked by addition of H2O2 to normoxic cells, and the oxygen-induced expression of VCAM-1 but not of ICAM-1 was inhibited by addition of the free radical scavengers superoxide dismutase, N-acetyl-L-cysteine, and pyrrolidinedithiocarbamate. These data indicate that an increase in oxygen availability stimulates ICAM-1 and VCAM-1 expression on micro- and macrovascular EC, which may contribute to adhesion and transmigration of different leukocyte populations in ischemia-reperfusion injuries.
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PMID:Increases in oxygen tension stimulate expression of ICAM-1 and VCAM-1 on human endothelial cells. 1036 86

The mechanisms by which sublethal doses of endotoxin protect against hyperoxic lung injury are not completely understood. We hypothesized that endotoxin treatment would result in a decreased inflammatory response to hyperoxia and that this would be accompanied by activation of neutrophils (as evidenced by loss of L-selectin) in the peripheral circulation. Adult rats were injected with endotoxin 0.5 mg/kg prior to and 24 hr after onset of exposure to > or = 98% O2. After 56 hr of hyperoxia, pulmonary neutrophils were lower in the O2/endotoxin group compared to O2 controls as measured by myeloperoxidase in lung homogenates and neutrophil counts in bronchoalveolar lavage fluid. Circulating neutrophils were also significantly lower in the O2/endotoxin group compared to O2 controls at 56 hr. Expression of the neutrophil adhesion molecule, L-selectin, was lower at 4 and 24 hr in the endotoxin-treated rats compared to O2 controls. There were no differences at 48 hr. Expression of CD18 rose significantly in the O2/endotoxin group after 4 hr, but thereafter did not differ from O2 controls. In summary, endotoxin protection from O2 toxicity was associated with reduced neutrophils in the lung and a loss of L-selectin from peripheral blood neutrophils.
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PMID:Endotoxin protection from oxygen toxicity: effect on pulmonary neutrophils and L-selectin. 1223 67

Chronic lung injury in the neonate is termed bronchopulmonary dysplasia (BPD). These patients generally require supplemental oxygen therapy, and hyperoxia has been implicated in the pathogenesis of BPD. The concomitant use of oxygen and inhaled NO (iNO) may result in the generation of reactive nitrogen species or may have an anti-inflammatory effect in the neonatal lung. We tested the hypothesis that exposure to >95% O2 in neonatal mice would increase trafficking of leukocytes into the lung and that the addition of iNO to >95% O2 would decrease this leukocyte trafficking. Hyperoxia resulted in fewer alveoli, increased presence of neutrophils and macrophages, and decreased number of mast cells within the lung parenchyma. Adding iNO to hyperoxia prevented the hyperoxia-induced changes and resulted in the numbers of alveoli, neutrophils, macrophages, and mast cells approximating those found in controls (room air exposure). Intercellular adhesion molecule (ICAM) and monocyte chemotactic protein-1 (MCP-1), two factors responsible for leukocyte recruitment, were up-regulated by hyperoxic exposure, but the addition of iNO to the hyperoxic exposure prevented the hyperoxia-induced up-regulation of ICAM and MCP-1. These data demonstrate that iNO alters the hyperoxia-induced recruitment of leukocytes into the lung.
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PMID:Inhaled nitric oxide decreases leukocyte trafficking in the neonatal mouse lung during exposure to >95% oxygen. 1991 14

Inhaled nitric oxide is being evaluated as a preventative therapy for patients at risk for bronchopulmonary dysplasia (BPD). Nitric oxide (NO), in the presence of superoxide, forms peroxynitrite, which reacts with tyrosine residues on proteins to form 3-nitrotyrosine (3-NT). However, NO can also act as an antioxidant and was recently found to improve the oxidative balance in preterm infants. Thus, we tested the hypothesis that the addition of a therapeutically relevant concentration (10 ppm) of NO to a hyperoxic exposure would lead to decreased 3-NT formation in the lung. FVB mouse pups were exposed to either room air (21% O(2)) or >95% O(2) with or without 10 ppm NO within 24 h of birth. In the first set of studies, body weights and survival were monitored for 7 days, and exposure to >95% O(2) resulted in impaired weight gain and near 100% mortality by 7 days. However, the mortality occurred earlier in pups exposed to >95% O(2) + NO than in pups exposed to >95% O(2) alone. In a second set of studies, lungs were harvested at 72 h. Immunohistochemistry of the lungs at 72 h revealed that the addition of NO decreased alveolar, bronchial, and vascular 3-NT staining in pups exposed to both room air and hyperoxia. The lung nitrite levels were higher in animals exposed to >95% oxygen + NO than in animals exposed to >95% oxygen alone. The protein levels of myeloperoxidase, monocyte chemotactic protein-1, and intracellular adhesion molecule-1 were assessed after 72 h of exposure and found to be greatest in the lungs of pups exposed to >95% O(2). This hyperoxia-induced protein expression was significantly attenuated by the addition of 10 ppm NO. We propose that in the presence of >95% O(2), peroxynitrite formation results in protein nitration; however, adding excess NO to the >95% O(2) exposure prevents 3-NT formation by NO reacting with peroxynitrite to produce nitrite and NO(2). We speculate that the decreased protein nitration observed with the addition of NO may be a potential mechanism limiting hyperoxic lung injury.
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PMID:Inhaled nitric oxide prevents 3-nitrotyrosine formation in the lungs of neonatal mice exposed to >95% oxygen. 2023 91

Patients with acute lung injury or respiratory distress syndrome often require supplemental oxygen to maintain tissue oxygenation; however, this treatment can cause or worsen lung inflammation. CD44 is a transmembrane adhesion molecule that is present on a wide variety of cell types, including leukocytes and parenchymal cells, and is an important player in leukocyte trafficking. The aim of this study was to determine the role of CD44 during hyperoxia-induced (> 95% oxygen) acute lung injury. Whereas all wild-type mice survived the 72-hour observation period, 37.5% of CD44 knockout (KO) mice died. CD44 deficiency was associated with a profound influx of neutrophils into the bronchoalveolar space, in the presence of similar or even lower neutrophil numbers in lung parenchyma, suggesting that CD44 is important for containing neutrophils in the pulmonary interstitium during hyperoxia. In addition, CD44 deficiency resulted in increased IL-6 and keratinocyte-derived chemokine release into bronchoalveolar lavage fluid (BALF). CD44 KO mice further displayed evidence for increased vascular leak and injury of type II respiratory epithelial cells. CD44 protected against bronchial epithelial cell death, as shown by increased epithelial cell necrosis and a trend toward increased BALF nucleosome levels in CD44 KO mice. CD44 can bind and internalize hyaluronic acid (HA), which acts proinflammatory. Concentrations of HA increased in BALF from CD44 KO but not wild-type mice during hyperoxia. These data suggest that CD44 protects against hyperoxia-induced lung injury and mortality by a mechanism that at least in part relies on its ability to clear HA from the bronchoalveolar space.
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PMID:CD44 is protective during hyperoxia-induced lung injury. 2046 90


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