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Query: UMLS:C0034063 (pulmonary edema)
 10,665 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)
Am J Respir Cell Mol Biol 1993 Oct
PMID:Increases in lung tissue expression of intercellular adhesion molecule-1 are associated with hyperoxic lung injury and inflammation in mice. 810 35

There is evidence supporting the role of active transport of Na+ in the resolution of pulmonary edema, but the exact cellular mechanism(s) underlying this process remain unknown. This study demonstrated the presence of ion channels on adult rat alveolar type II cells that might be associated with this active transport of Na+. Patch-clamp techniques were used to characterize a nonselective cation channel in adult rat alveolar type II epithelial cells held in culture for 24 to 72 h. Single-channel currents were recorded from inside-out, cell-free membrane patches. The most common type of single channel had a linear slope conductance of 20.4 +/- 0.6 pS (n = 22) in symmetrical NaCl (150 mM) solutions. The channel was approximately equally permeable to Na+ and K+ ions (PK/PNa = 1.15) and was highly selective for cations (PCl/PNa < 0.05). Channel activity was Ca(2+)-dependent, and it required at least 10 microM Ca2+ on the cytosolic side of an inside-out patch to activate the channel. Amiloride (1 to 10 microM), a Na+ channel blocker in epithelial tissue, reduced the steady-state open probability of the channel 10-fold but had no significant effect on the magnitude of the single-channel conductance. Single channels with similar properties were not found in cultured rat alveolar macrophages. The possible role of this amiloride-sensitive, nonselective cation channel in Na+ transport and lung liquid clearance is discussed.
Am J Respir Cell Mol Biol 1993 Sep
PMID:Identification of nonselective cation channels in cultured adult rat alveolar type II cells. 839 61

Diesel engine-powered vehicles emit some 30 to 100 times more particles than do gasoline engine cars. We previously reported that diesel exhaust particles (DEP) instilled intratracheally into mouse caused lung edema accompanying endothelial cell damage. In order to clarify further the biological effects of DEP on the respiratory system, the primary target of DEP instillation, we examined the direct action of DEP on isolated tissues and the cytotoxicity of DEP on cultured cells of respiratory tracts in guinea pigs. DEP were collected on glass fiber filters from a light-duty (2730 cc), four cylinder diesel engine. DEP induced a dose-dependent relaxation in tracheal smooth muscle and lung parenchymal preparations from guinea pigs. Neither propranolol nor ranitidine inhibited the relaxing effect of DEP on tracheal preparations. DEP also exhibited concentration- and time-dependent cytotoxicity on cultured tracheal smooth muscle cells and lung fibroblasts from guinea pigs, as assessed by specific [51Cr] release. These cytotoxicities induced by DEP were significantly inhibited by catalase, deferoxamine and MK-447, whereas SOD and mannitol had little effect. These inhibitory effects were blunted by the higher concentration of DEP. These results suggest that the cytotoxicity of DEP may cause dysfunction of respiratory tissues, which are mediated via oxygen radicals, probably hydroxyl radicals or hydrogen peroxides.
Res Commun Mol Pathol Pharmacol 1995 Nov
PMID:Biological effects of diesel exhaust particles (DEP) on tissues and cells isolated from respiratory tracts of guinea pigs. 874 91

We examined the effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), on mortality, morbidity, and cardiovascular parameters following traumatic brain injury (TBI) in the rat. Rats were anesthetized with 2% isoflurane prior to moderate (2.0 atmosphere), central fluid percussion TBI. Temporalis muscle temperature was maintained at 37 +/- 0.5 degrees C. L-NAME (10 mg/kg iv) was administered once at either 5 min before, 5 min after, or 15 min after TBI. Sensorimotor deficits and spatial learning/ memory deficits were assessed after injury. Separate groups of rats were monitored for cardiovascular parameters. Preinjury administration of L-NAME significantly increased mortality from 13 (vehicle) to 70% (associated with pulmonary edema), whereas postinjury, L-NAME had no effect on mortality (14 and 25%). L-NAME administered at 5 or 15 min after injury had no significant effect on motor performance or cognitive performance deficits associated with TBI. L-NAME in uninjured rats increased arterial blood pressure by 25 mmHg within 2 min. L-NAME injected 5 min before TBI greatly prolonged the hypertensive episode associated with TBI (1 min in vehicle vs 60 min in L-NAME). L-NAME injected 5 min after TBI caused a sustained 35 mmHg increase in blood pressure. These findings suggest that acute inhibition of NOS has detrimental consequences on mortality that may be owing to its cardiovascular effects.
Mol Chem Neuropathol
PMID:Inhibition of nitric oxide synthase potentiates hypertension and increases mortality in traumatically brain-injured rats. 913 24

Clara cell secretory protein (CCSP) is an abundant component of the extracellular lining fluid of airways. Even though the in vivo function of CCSP is unknown, in vitro studies support a potential role of CCSP in the control of inflammatory responses. CCSP-deficient mice (CCSP -/-) were generated to investigate the in vivo function of this protein (13). In this study, we used hyperoxia exposure as a model to investigate phenotypic consequences of CCSP deficiency following acute lung injury. The pathologic response of the mouse lung to hyperoxia, and recovery of the lung, include inflammatory cell infiltrate and edema. Continuous exposure to > 95% O2 was associated with significantly reduced survival time among CCSP -/- mice as compared with strain-, age-, and sex-matched wild-type control mice. Differences in survival were associated with early onset of lung edema in CCSP -/- mice as compared with wild-type controls. To further investigate these differences in response, mice were exposed to > 95% O2 for either 48 h or 68 h with one group receiving 68 h of hyperoxia followed by room-air recovery. Lung RNA was characterized for changes in the abundance of cytokine messenger RNA (mRNA) using a ribonuclease (RNase) protection assay. After 68 h of hyperoxia, interleukin-6 (IL-6), IL-1beta, and IL-3 mRNAs were 14-, 3-, and 2.5-fold higher, respectively, in CCSP -/- mice than in similarly exposed wild-type control mice. Increased expression of IL-1beta mRNA in hyperoxia-exposed CCSP -/- mice was localized principally within the lung parenchyma, suggesting that the effects of CCSP deficiency were not confined to the airway epithelium. We conclude that CCSP deficiency results in increased sensitivity to hyperoxia-induced lung injury as measured by increased mortality, early onset of lung edema, and induction of proinflammatory cytokine mRNAs.
Am J Respir Cell Mol Biol 1997 Aug
PMID:Altered pulmonary response to hyperoxia in Clara cell secretory protein deficient mice. 927 2

Decrease in alveolar oxygen tension may induce acute lung injury with pulmonary edema. We investigated whether, in alveolar epithelial cells, expression and activity of epithelial sodium (Na) channels and Na,K-adenosine triphosphatase, the major components of transepithelial Na transport, were regulated by hypoxia. Exposure of cultured rat alveolar cells to 3% and 0% O2 for 18 h reduced Na channel activity estimated by amiloride-sensitive 22Na influx by 32% and 67%, respectively, whereas 5% O2 was without effect. The decrease in Na channel activity induced by 0% O2 was time-dependent, significant at 3 h of exposure and maximal at 12 and 18 h. It was associated with a time-dependent decline in the amount of mRNAs encoding the alpha-, beta-, and gamma-subunits of the rat epithelial Na channel (rENaC) and with a 42% decrease in alpha-rENaC protein synthesis as evaluated by immunoprecipitation after 18 h of exposure. The 0% O2 hypoxia also caused a time-dependent decrease in (1) ouabain-sensitive 86Rubidium influx in intact cells, (2) the maximal velocity of Na,K-ATPase on crude homogenates, and (3) alpha1- and beta1-Na,K-ATPase mRNA levels. Levels of rENaC and alpha1-Na,K-ATPase mRNA returned to control values within 48 h of reoxygenation, and this was associated with complete functional recovery. We conclude that hypoxia induced a downregulation of expression and activity of epithelial Na channels and Na,K-ATPase in alveolar cells. Subsequent decrease in Na reabsorption by alveolar epithelium could participate in the maintenance of hypoxia-induced alveolar edema.
Am J Respir Cell Mol Biol 1997 Oct
PMID:Hypoxia downregulates expression and activity of epithelial sodium channels in rat alveolar epithelial cells. 937 26

Increased microvascular permeability and mucosal edema are pathological features of airway inflammation in asthma. In this study, we investigated the characteristics of the edema response occurring in a model of antigen-induced lung inflammation in sensitized brown Norway rats and examined the effects of monoclonal antibodies (mAbs) to adhesion molecules on this response. Ovalbumin (OA) challenge-induced increases in lung permeability were determined by the leakage of 125I-labeled bovine serum albumin (BSA) into the extravascular tissues of the lungs 24 h after challenge in animals intravenously injected (prechallenge) with this tracer. Inflammatory cell infiltration into the alveolar space was determined by bronchoalveolar lavage (BAL). Mean extravascular plasma volume in the lung increased 233% as compared with control (P < 0.005) at 24 h and increased to 517% by 72 h. The 24-h edema response was completely inhibited by two oral doses (0.1 mg/kg) of dexamethasone 1 h before, and 7 h after, challenge. Intraperitoneal administration of the anti-rat ICAM-1 mAb 1A29, or anti-rat alpha4 integrin mAb TA-2 (2 mg/kg at 12 and 1 h before, and 7 h after, antigen challenge), significantly suppressed eosinophil infiltration into the alveolar space without inhibiting the enhanced microvascular leakage and lung edema. Determination of plasma antibody concentrations by ELISA of mouse IgG1 indicated that sufficient concentrations of the appropriate mAb were present to block alpha4- or ICAM-1-dependent adhesion. The results suggest that increases in microvascular permeability and plasma leakage occurred independently of eosinophil accumulation.
Am J Respir Cell Mol Biol 1997 Dec
PMID:Roles of adhesion molecules ICAM-1 and alpha4 integrin in antigen-induced changes in microvascular permeability associated with lung inflammation in sensitized brown Norway rats. 940 63

Previous studies have shown that a single exposure of animals to ozone (O3) can induce protection or adaptation to the acute injurious effects of a subsequent O3 challenge. Although a number of mechanisms have been proposed to account for this response, none appear to be fully explanatory. We examined the role interleukin (IL)-6 may play in the induction of adaptation to O3-induced pulmonary injury. A statistically significant 29-fold increase in bronchoalveolar lavage fluid IL-6 levels was observed in rats exposed to 0.5 ppm O3 during nighttime hours when compared with daytime hours even though similar kinetics of inflammation were induced by each exposure. Animals receiving an initial nighttime O3 exposure showed a lesser degree of inflammation following a subsequent O3 exposure when compared with animals which received an initial daytime exposure. Rats pretreated with IL-6 both intratracheally and intraperitoneally and subsequently exposed to O3 showed a lesser degree of cellular inflammation when compared with respective controls. Pretreatment of rats with anti-IL-6-receptor antibodies (ra) prior to the nighttime O3 exposure completely abrogated the O3-induced cellular adaptive response without effecting the inflammatory response induced by the initial nighttime O3 exposure. In fact, administration of anti-IL-6ra augmented the neutrophil influx following the second O3 exposure. Anti-IL-6ra treatment did not alter the pulmonary edema adaptive response, suggesting that the O3-induced cellular and edema adaptive responses are regulated by different mechanisms. Our data indicate that mobilization of pulmonary antioxidants does not play a role in the IL-6-mediated early cellular adaptive response and suggest that IL-6 is an essential mediator of the O3-induced cellular adaptive response.
Am J Respir Cell Mol Biol 1998 May
PMID:Cytokine mediation of ozone-induced pulmonary adaptation. 956 40

The mechanism by which pertussis toxin (Ptx) causes lung edema is not clear. We investigated the role of pulmonary manganese superoxide dismutase (MnSOD) and protein kinase C (PKC) in Ptx-induced lung edema. We demonstrated that intraperitoneal injection of Ptx at a concentration of 5 microg/100 g body weight caused a similar degree of lung edema in 2 d, as measured by lung wet weight/dry weight ratio, in heterozygous MnSOD gene (Sod2)-knockout mice (Sod2(+/-)) and in their wild-type littermates (Sod2(+/+)). The level of lung MnSOD activity in Sod2(+/-) mice was approximately half that of Sod2(+/-) mice. Ptx had no effect on levels of lung MnSOD messenger RNA, immunoreactive protein, or enzyme activity in either Sod2(+/+) or Sod2(+/-) mice. Ptx also had no effect on lung copper-zinc SOD, catalase, and glutathione peroxidase activities in these mice. On the other hand, Ptx caused the activation of lung PKC, for example, by translocation of a 72-kD PKC isoform from the cytosolic fraction to the membrane fraction. Pretreatment of mice with bisindolylmaleimide, a PKC inhibitor, prevented both the Ptx-induced activation of PKC and lung edema. These data suggest that Ptx-induced lung edema in mice is, at least in part, due to the activation of lung PKC.
Am J Respir Cell Mol Biol 1999 Mar
PMID:Pertussis toxin-induced lung edema. Role of manganese superoxide dismutase and protein kinase C. 1003 Aug 45

Two genes encode proteins with prostaglandin G/H synthase (PGHS) activity. PGHS-1 is primarily a constitutively expressed gene, whereas inflammatory agents such as bacterial lipopolysaccharide (LPS) endotoxin rapidly induce the PGHS-2 gene in leukocytes. Both PGHS-1 and PGHS-2 are rate-limiting enzymes for the production of prostaglandins and thromboxane following release of arachidonic acid by phospholipases. We previously reported that LPS perfusion into the circulation of isolated perfused rabbit lung (IPL) results in thromboxane-dependent pulmonary hypertension and lung edema when the LPS-primed lung is subsequently stimulated with platelet activating factor (PAF) (J. Clin. Invest. 1990;85:1135). In this study, we showed that the mechanism by which LPS primes IPL for enhanced production of thromboxane and pulmonary hypertension in response to PAF depends on specific upregulation of the PGHS-2 gene in the rabbit lung. LPS perfusion of IPL induced PGHS-2 gene expression, which correlated with the conversion of free arachidonic acid to thromboxane-B2 (TXB2) and the onset of pulmonary hypertension. LPS-induced PGHS-2 expression, TXB2 release, and pulmonary hypertension were inhibited by actinomycin D (an inhibitor of transcription) and cycloheximide (an inhibitor of protein synthesis). The constitutively expressed PGHS-1 remained unchanged with LPS perfusion, and did not convert free arachidonic acid to TXB2, suggesting that PGHS-1 does not contribute to the induction of pulmonary hypertension by LPS. These studies reveal a pathogenic role for induction of PGHS-2 in lung injury.
Am J Respir Cell Mol Biol 1999 Mar
PMID:Bacterial lipopolysaccharide induction of the prostaglandin G/H synthase 2 gene causes thromboxane-dependent pulmonary hypertension in rabbits. 1003 Aug 48


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