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

The present study is the first investigation to demonstrate, by employing the combined approach of immunologically and electron microscope methods, the presence of actin-like contractile proteins in the mammalian retina, the corneal epithelium and endothelium, the iris, and the ciliary body, and to confirm their presence in lens epithelium. This is also the first report to demonstrate by these methods the presence of microfilaments and intermediate filaments in retinal vascular endothelium. Since we have shown that actin filaments are especially abundant in immature retinal endothelial cells, the question of their function arises, and we have discussed their possible relevance to the closure of immature retinal vessels when exposed to hyperoxia.
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PMID:Contractile proteins in retinal endothelium and other non-muscle tissues of the eye. 36 Oct 70

The pulmonary endothelium is known to be sensitive to oxidant injury, including that of hyperoxia. Similar to effects of exposure to 80-95% O2, porcine platelet transforming growth factor (TGF)-beta 1 at concentrations of greater than or equal to 0.3 ng/ml inhibited proliferation and caused enlargement of bovine pulmonary artery endothelial cells after 24 h of incubation in room air. Uptake of [3H]thymidine, but not of [3H]deoxycytidine, was suppressed by both hyperoxia and TGF-beta 1. The cellular enlargement produced by TGF-beta 1 in room air was attenuated in the presence of anoxia, indicating a need for O2 for TGF-beta 1 to have an effect on cell size. In the presence of 20 microM FeCl3, both TGF-beta 1 and 80% O2 produced marked cellular desquamation from culture dishes. The antioxidants dimethyl sulfoxide and vitamin E partially counteracted the growth inhibitory effect of TGF-beta 1 on endothelial cells. In contrast to its effect on endothelial cells, TGF-beta 1 only moderately altered size and proliferation of smooth muscle cells from the same pulmonary vessels. Uptake of [3H]thymidine by smooth muscle cells was uninfluenced in 48 h by TGF-beta 1, and little, if any, desquamation of these cells occurred with TGF-beta 1 in the presence of 20 microM FeCl3. We propose from these experiments that TGF-beta 1 may produce an oxidant effect on vascular endothelium that is capable of causing injury to this tissue.
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PMID:TGF-beta 1 produces a "prooxidant" effect on bovine pulmonary artery endothelial cells in culture. 192 58

Eight monkeys were anesthetized with ketamine hydrochloride and positive pressure ventilated with greater than 95% oxygen (tests) or room air (controls) for 24 hours. Two test monkeys and one control were treated with E. coli endotoxin (500 micrograms/kg) IV at the start of the study and after 12 hours. Histopathological changes in the lung parenchyma were evaluated using light and electron microscopy. Interstitial edema was detected as early as 24 hours after the onset of hyperoxia but there was no significant increase in the alveolar-capillary distance (blood-air barrier). Morphologic signs of oxygen toxicity further included swelling and disruption of vascular endothelium, and swelling of alveolar Type II pneumocytes. There was no difference in the number of macrophages per high power field between the four groups but significant differences were observed in the number of neuroepithelial bodies (NEBs) per cm2 and mast cells per high power field at the light microscopic level. Treatment with endotoxin did not protect against oxygen toxicity and was associated with an exacerbation of the morphological alterations in the lung parenchyma and swelling of alveolar Type I pneumocytes.
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PMID:Oxygen toxicity in the infant rhesus monkey lung. Light microscopic and ultrastructural studies. 298 Jan 4

Recent work with isolated blood vessels has emphasized the importance of intact endothelium when the relaxation of vascular smooth muscle is induced by acetylcholine (ACh). However, the physiologic significance of this endothelial-dependent ACh response in a complete organ circulation is unclear. We questioned whether diminished ACh vasodilation would result from damage of lung vascular endothelium and whether this response could be used as an indication of endothelial injury. We therefore induced pulmonary endothelial cell injury in one rat model by repeated injections of alpha-naphthyl thiourea (ANTU) and in a second rat model by exposing rats for 52 h to 100% oxygen at a barometric pressure of 760 torr (hyperoxia). Rats injected with Tween 80, the solvent for ANTU, or exposed to ambient Denver air served as the respective control animals. The isolated lungs of these rats were perfused with a recirculating cell- and plasma-free, physiological salt solution to study the effect of ACh or NaCl infusion on pulmonary perfusion pressure and vascular responsiveness. ANTU-treated rats demonstrated an intact vasodilatory response after ACh infusion when compared with the solvent control animals. The immediate pulmonary vasodilation after ACh infusion was slightly enhanced in the hyperoxic rat lung when compared with the rats exposed to ambient air, but there was no difference between these groups in the prolonged depression of vascular responsiveness to hypoxia or angiotensin II. Thus, in both models of lung endothelial cell injury, the pulmonary vascular responses to ACh were intact.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acetylcholine-induced pulmonary vasodilation in lung vascular injury. 300 69

Vascular inflammatory response to hyperoxia (FIO2 greater than 0.98) was studied in awake jugular and carotid catheterized rats. Simultaneous i.v. injection of 125I albumin (125I A), 99mTc polymorphonuclear cells (99mTc PMN) and 51Cr red blood cells (51Cr RBC) allowed to study both the macromolecule exchange through vascular endothelium and the leukocyte uptake by several organs (liver, lungs, spleen) with respect to radiolabelled red blood cells, as an intravascular reference. Rats were exposed to O2 for 24, 38 and 45 h. They were anesthetized and killed by exanguination 15 to 120 min following the tracer injection. After 45 h exposure, the plasmatic 125I A half-life decreased significantly (158 +/- 42 min for the control; 106 +/- 34 min for the exposed animals). The ratio 125I A/51Cr RBC varied significantly in the lung. The iodinated albumin exchange through lung vascular endothelium was altered at the 24th h, with a significant difference reached by the 45th h. At the same time, the pulmonary decreasing curve of 99mTc/51Cr RBC ratio versus time was not not modified. In our experimental conditions, there was no detectable variation in the lung uptake and vascular transit of PMN cells. The discussion of the results must be related with the technics used in the present work when the albumin exchange increased.
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PMID:[Albumin exchange and polymorphonuclear vascular transit in hyperoxic pulmonary oedema in awake rats]. 688 53

Destruction of pulmonary endothelial cells is characteristic of hyperoxic lung injury. During recovery from hyperoxia, pulmonary endothelial cells proliferate to regenerate the vascular endothelium. Vascular endothelial growth factor (VEGF) is a peptide growth factor that is mitogenic specifically for endothelial cells. We hypothesized that VEGF messenger RNA (mRNA) increases during recovery from acute hyperoxic lung injury. Adult rabbits were exposed to 100% oxygen for 64 h and allowed to recover in air for 0, 1, 3, and 5 days. In situ hybridization showed increased VEGF expression in alveolar epithelial cells beginning at 1 day recovery. By 3 days recovery the message was in alveolar epithelial cells throughout the lung. Compared with alveolar epithelial cells, little or no expression was noted in large vessel endothelial cells, airway cells, or smooth muscle cells. Combined in situ hybridization for VEGF and immunostaining for macrophages and other mesenchymal cells found no VEGF message in those cell types. Isolated alveolar macrophages had no detectable VEGF message. Cells expressing VEGF mRNA were enriched in alveolar type II cell preparations from recovering lung. Double in situ hybridization for VEGF and surfactant protein-C (SP-C) showed co-expression in a population of type II cells, but with an inverse relationship: cells with abundant VEGF mRNA did not have abundant SP-C mRNA. Type II cells in vitro expressed VEGF message, but only when the SP-C message abundance was relatively low. We conclude that alveolar type II cells express increased VEGF mRNA during recovery from acute hyperoxia. These findings are consistent with a role for VEGF in regulating microvascular endothelial repair after oxidant injury.
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PMID:Vascular endothelial growth factor mRNA increases in alveolar epithelial cells during recovery from oxygen injury. 754 67

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

Metallothionein (MT) is a low-molecular-weight cysteine-rich protein with extensive metal binding capacity and potential nonenzymatic antioxidant activity. Despite the sensitivity of vascular endothelium to either heavy metal toxicity or oxidative stress, little is known regarding the role of MT in endothelial cells. Accordingly, we determined the sensitivity of cultured sheep pulmonary artery endothelial cells (SPAEC) that overexpressed MT to tert-butyl hydroperoxide (t-BOOH), hyperoxia, or 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN; peroxyl radical generator). Nontoxic doses of 10 microM Cd increased MT levels from 0.21 +/- 0.03 to 2.07 +/- 0.24 microg/mg and resulted in resistance to t-BOOH and hyperoxia as determined by reduction of Alamar blue or [3H]serotonin transport, respectively. SPAEC stably transfected with plasmids containing either mouse or human cDNA for MT were resistant to both t-BOOH and hyperoxia. In addition, we examined transition metal-independent, noncytotoxic AMVN-induced lipid peroxidation after metabolic incorporation of the oxidant-sensitive fluorescent fatty acid cis-parinaric acid into phospholipids and high-performance liquid chromatography separation. SPAEC that overexpressed MT after gene transfer completely inhibited peroxyl oxidation of phosphatidylserine, phosphatidylcholine, and sphingomyelin (but not phosphatidylethanolamine) noted in wild-type SPAEC. These data show for the first time that MT can 1) protect pulmonary artery endothelium against a diverse array of prooxidant stimuli and 2) directly intercept peroxyl radicals in a metal-independent fashion, thereby preventing lipid peroxidation in intact cells.
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PMID:Overexpression of metallothionein decreases sensitivity of pulmonary endothelial cells to oxidant injury. 935 62

Intercellular adhesion molecule-1 (ICAM-1) of the vascular endothelium plays a key role in the development of pulmonary oxygen toxicity. We studied the effect of steroid on hyperoxia-induced ICAM-1 expression using cultured endothelial cells in vitro. Human pulmonary artery endothelial cells (HPAECs) were cultured to confluence, and then the monolayers were exposed to either control (21% O(2)-5% CO(2)) or hyperoxic (90% O(2)-5% CO(2)) conditions with and without a synthetic glucocorticoid, methylprednisolone (MP). MP reduced hyperoxia-induced ICAM-1 and ICAM-1 mRNA expression in a dose-dependent manner. Neutrophil adhesion to hyperoxia-exposed endothelial cells was also inhibited by MP treatment. In addition, MP attenuated hyperoxia-induced H(2)O(2) production in HPAECs as assessed by flow cytometry. An electrophoretic mobility shift assay demonstrated that hyperoxia activated nuclear factor-kappaB (NF-kappaB) but not activator protein-1 (AP-1) and that MP attenuated hyperoxia-induced NF-kappaB activation dose dependently. With Western immunoblot analysis, IkappaB-alpha expression was decreased by hyperoxia and increased by MP treatment. These results suggest that MP downregulates hyperoxia-induced ICAM-1 expression by inhibiting NF-kappaB activation via increased IkappaB-alpha expression.
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PMID:Effect of steroid on hyperoxia-induced ICAM-1 expression in pulmonary endothelial cells. 1066 7

Monocyte chemoattractant protein-1 (MCP-1), acting through its C-C chemokine receptor 2 (CCR-2), has important roles in inflammation, angiogenesis, and wound repair. The individual and combined effects of inhaled nitric oxide (NO) and hyperoxia on lung MCP-1 and CCR-2 in relation to lung leukocyte dynamics are unknown. Because MCP-1 gene is up-regulated by oxidants, we hypothesized that inhaled NO with hyperoxia will increase MCP-1 production and CCR-2 expression more than either gas alone. We randomly assigned young piglets to breathe room air (RA), RA+50 ppm NO (RA+NO), O(2), or O(2)+NO for 1 or 5 d before sacrifice. Lungs were lavaged and tissues preserved for hybridization studies, Western blotting, histology, and immunohistochemistry. The results show that lung MCP-1 production and alveolar macrophage count were significantly elevated in the 5-d O(2) and O(2)+NO groups relative to the RA group (p < or = 0.05). In contrast, lung CCR-2 abundance was diminished in the O(2) group (p </= 0.05), but not in the O(2)+NO group, compared with the RA group. No difference was detected in any variable studied at 24 h. CCR-2 distribution was similar in all groups with staining of alveolar septa, macrophages, vascular endothelium, and the luminal epithelial surface of airways. We conclude that although hyperoxia increases MCP-1 in young piglet lungs, it also decreases CCR-2 abundance, which may limit participation of MCP-1 in alveolar macrophage recruitment. Inhaled NO, unlike hyperoxia, has no significant independent effect, but its concurrent administration during hyperoxia attenuates the decremental effect of hyperoxia on CCR-2 abundance.
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PMID:Monocyte chemoattractant protein-1 and its receptor CCR-2 in piglet lungs exposed to inhaled nitric oxide and hyperoxia. 1164 60


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