Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenesis of pulmonary oxygen toxicity is postulated to be related in part to neutrophil-mediated injury. This study examined the effect of a monoclonal antibody directed against the CD11a,b,c/CD18 glycoprotein complex (beta 2 leukocyte integrins) on oxygen-induced lung injury. M8, a monoclonal antibody that binds to the beta chain of the guinea pig leukocyte integrins that facilitate neutrophil adherence to vascular endothelium, was injected into adult guinea pigs prior to and during exposure to > 98% oxygen. Control oxygen-exposed animals were injected with a noninhibitory antibody to the CD18 complex or with saline. Survival in oxygen was similar for animals treated with M8 when compared with those treated with saline (102 versus 105 h, respectively, NS). Pulmonary edema as assessed by protein in the supernatant of bronchoalveolar lavage fluid (BALF) was higher in the three groups of oxygen-exposed animals than in the air-exposed groups (p < 0.01), but it did not differ between the M8 antibody treatment group and the other oxygen-exposed groups. M8 antibody treatment did not decrease hyperoxia-induced neutrophil accumulation into the lung as assessed by myeloperoxidase activity (MPO) in lung homogenates or by neutrophil counts in histologic specimens. M8 antibody also did not decrease neutrophil counts or MPO in alveolar lavage fluid, both of which were significantly elevated in all oxygen-exposed groups. These results suggest that hyperoxia-induced neutrophil migration into the lung and acute lung injury occurs by CD18-independent processes in the guinea pig model of pulmonary oxygen toxicity.
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PMID:Oxygen-induced lung injury in the guinea pig proceeds through CD18-independent mechanisms. 790 67

We studied the effects of inhibiting and augmenting neutrophil function by using an immunocompetent rat model of infectious and hyperoxic lung injury. After intrabronchial Escherichia coli challenge at all fractional inspired O2 (FIO2) values studied (FIO2 = 0.21, 0.60, and 0.95) and after lethal O2 exposure alone (FIO2 = 0.90), lung injury, as measured by histological and physiological changes, was reduced by a CD11b/CD18-directed monoclonal antibody (MAb 1B6, P < 0.05 vs. controls) but was increased by recombinant granulocyte colony-stimulating factor (rG-CSF; P < 0.05 vs. control; MAb 1B6 vs. rG-CSF, P < 0.004). Pulmonary neutrophil counts were reduced by MAb 1B6 (P < 0.04) and increased by rG-CSF (P < 0.0004) compared with control animals. However, despite antibiotics, MAb 1B6 and rG-CSF both significantly increased the relative risk of death, independent of O2 concentration, during E. coli pneumonia (1.74 [symbol: see text] 1.20 and 2.39 [symbol: see text] 1.19, respectively, each P < 0.01). During lethal hyperoxia, MAb 1B6 increased the relative risk of death (1.76 [symbol: see text] 1.28, P < 0.16), whereas rG-CSF had no effect on survival (0.97 [symbol: see text] 1.28, P = 0.89). Thus inhibition of neutrophil function attenuated and enhancement worsened lung injury in response to infectious and hyperoxic challenges, supporting a pathophysiological role of the neutrophil in these processes. However, it is problematic that MAb 1B6 therapy, despite preventing lung damage, ultimately worsened host defenses and survival. Furthermore, rG-CSF also adversely affected survival during infectious lung injury, demonstrating the inherent risks of inhibiting or augmenting neutrophil function in an immunocompetent host during infection.
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PMID:Controlled trials of rG-CSF and CD11b-directed MAb during hyperoxia and E. coli pneumonia in rats. 880 15

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

Clinical use of nitric oxide (NO) is usually in conjunction with high oxygen concentrations, the effects of which may include lung neutrophil accumulation, apoptosis and upregulation of antioxidant enzyme activity. To define the effects of NO on neutrophils from young piglets and its relationship to lung neutrophil dynamics during hyperoxia we exposed thirty piglets to room air (RA), RA+NO (50 ppm NO), O2 (FiO2> or =0.96) or O2+NO for 5 days. Ten additional animals breathed RA+NO or O2+NO, then recovered in RA for 3 days before sacrifice. Neutrophil CD18 and intracellular oxidant production were measured by flow cytometry. Lung apoptosis were assessed by TUNEL assay. Lung myeloperoxidase, SOD and catalase were measured biochemically. When compared to RA group, there was significant reduction in neutrophil CD18 and intracellular oxidant production in the RA+NO group, but lung MPO was unchanged. The O2 and O2+NO groups did not differ in CD18 expression or in intracellular oxidant production, but had significant increase in lung myeloperoxidase compared to the RA group. Apoptosis increased significantly only in the O2+NO group. The O2 group showed significantly increased lung SOD and catalase activity compared to the RA group, whereas the RA+NO and O2+NO groups did not. We conclude that inhaled NO at 50 ppm decreases neutrophil CD18 expression as well as intracellular oxidant production. However, this effect does not impact lung neutrophil accumulation during concurrent hyperoxia. The combination of NO and O2 exposure produces an increase in lung apoptosis. Finally, NO may prevent upregulation of SOD and catalase activity during hyperoxia, potentially increasing injury.
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PMID:Independent and combined effects of prolonged inhaled nitric oxide and oxygen on lung inflammation in newborn piglets. 1065 29

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

Neonatal rats have an increased tolerance to hyperoxia, which is associated with a diminished pulmonary inflammatory response compared with adults. To investigate this differing response, expression of the neutrophil adhesion molecules, L-selectin and CD18, and levels of soluble L-selectin, were examined using flow cytometry and sandwich enzyme-linked immunosorbent assay on air-exposed neonatal rat neutrophils at 0-24 and 72 h and 7, 10, 14, and 21 d of age compared with the adult and after exposure to hyperoxia (>/= 98% O2) for 56 h in adults and for 72 h and 7 d in neonates. Expression of L-selectin in 0-24-h neonates was similar to adults, but was significantly lower than adults at 72 h and 7 d (P = 0.011). Soluble L-selectin levels were significantly higher than those in adults in the 0-24- and 72-h neonates (P < 0.001). CD18 expression in unstimulated and activated neutrophils of neonatal rats was higher at 0-24 h than in the adult (P < 0.001), but thereafter did not differ from adults. After hyperoxic exposure, L-selectin did not differ between the exposure groups but soluble L-selectin tended to increase in neonates after 7 d of O2 exposure Finally, CD18 was significantly higher after hyperoxic exposure of the adult (P = 0.008), but did not change with oxygen exposure in the neonate. Based on these findings, we speculate that differences between neonatal and adult rats in expression of L-selectin may contribute to delayed oxygen toxicity in neonatal rats.
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PMID:Neutrophil adhesion molecule expression in the developing neonatal rat exposed to hyperoxia. 1273 74

Lung inflammation plays a key role in the pathogenesis of bronchopulmonary dysplasia (BPD), a chronic lung disease of premature infants. The challenge in BPD management is the lack of effective and safe antiinflammatory agents. Leukadherin-1 (LA1) is a novel agonist of the leukocyte surface integrin CD11b/CD18 that enhances leukocyte adhesion to ligands and vascular endothelium and thus reduces leukocyte transendothelial migration and influx to the injury sites. Its functional significance in preventing hyperoxia-induced neonatal lung injury is unknown. We tested the hypothesis that administration of LA1 is beneficial in preventing hyperoxia-induced neonatal lung injury, an experimental model of BPD. Newborn rats were exposed to normoxia (21% O2) or hyperoxia (85% O2) and received twice-daily intraperitoneal injection of LA1 or placebo for 14 days. Hyperoxia exposure in the presence of the placebo resulted in a drastic increase in the influx of neutrophils and macrophages into the alveolar airspaces. This increased leukocyte influx was accompanied by decreased alveolarization and angiogenesis and increased pulmonary vascular remodeling and pulmonary hypertension (PH), the pathological hallmarks of BPD. However, administration of LA1 decreased macrophage infiltration in the lungs during hyperoxia. Furthermore, treatment with LA1 improved alveolarization and angiogenesis and decreased pulmonary vascular remodeling and PH. These data indicate that leukocyte recruitment plays an important role in the experimental model of BPD induced by hyperoxia. Targeting leukocyte trafficking using LA1, an integrin agonist, is beneficial in preventing lung inflammation and protecting alveolar and vascular structures during hyperoxia. Thus, targeting integrin-mediated leukocyte recruitment and inflammation may provide a novel strategy in preventing and treating BPD in preterm infants.
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PMID:Efficacy of Leukadherin-1 in the Prevention of Hyperoxia-Induced Lung Injury in Neonatal Rats. 2590 34