Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the role of arachidonic acid-derived eicosanoids in staphylococcal alpha-toxin (alpha-T)-induced lung injury. Bolus injection of 200 and 500 micrograms alpha-T into isolated perfused rat lungs resulted in increased pulmonary perfusion pressure followed by lung weight gain. Inhibition of pressure change with papaverine (10(-4) M) failed to abolish lung edema. Furthermore, alpha-T increased the permeability-surface area product in papaverine-treated lungs and caused marked endothelial cell injury and interstitial edema as documented by electron microscopy. alpha-T dose dependently increased lung tissue thromboxane B2 (TxB2) levels and leukotriene C4 levels. In lungs given 0, 200, and 500 micrograms of alpha-T, TxB2 (in micrograms/g wet lung) values were 16.3 +/- 2.8, 25.0 +/- 3.0, and 54.2 +/- 6.2; and leukotriene C4 values were 4.6 +/- 1.1, 6.7 +/- 1.2, and 22.1 +/- 3.8, respectively. Inhibition of cyclooxygenase enzyme with indomethacin (10(-5) M) or lipoxygenase enzyme with 2(12-hydroxydodeca-5,10-dinyl)-3,5,6-trimethyl-1,4-benzoq uin one (AA861, 10(-5) M) attenuated the vasoconstriction and prevented lung edema due to low dose (200 micrograms) but not high dose (500 micrograms) alpha-T. The protective effect of these inhibitors on lung edema is in part due to decreases in alpha-T-stimulated venoconstriction because alpha-T-induced increase in lung microvascular pressure was attenuated by indomethacin and AA861 pretreatment. We conclude that both eicosanoid-dependent and eicosanoid-independent mechanisms contribute to alpha-T-induced lung edema in the rat.
 ...
PMID:Role of eicosanoids in staphylococcal alpha-toxin-induced lung injury in the rat. 156 64

Phosgene inhalation causes a severe noncardiogenic pulmonary edema characterized by an influx of neutrophils into the lung. To study the role of neutrophils in lung injury and mortality after phosgene, we investigated the effects of leukocyte depletion with cyclophosphamide, inhibiting the generation of the chemotaxin leukotriene B4 with the 5-lipoxygenase inhibitor AA861 and impairing neutrophil migration with the microtubular poison colchicine. Cyclophosphamide, AA861, and colchicine injected before exposure significantly reduced percent neutrophils, protein, and thiobarbituric acid-reactive products in bronchoalveolar lavage fluid of rats exposed to phosgene (0.5 ppm X 60 min). Cyclophosphamide, AA861, and colchicine also significantly decreased mortality from phosgene (2.0 ppm X 90 min) in mice. Colchicine significantly reduced neutrophil influx, lung injury, and mortality even when given 30 min after phosgene exposure. We conclude that lung injury and mortality after phosgene exposure are associated with an influx of neutrophils into the lung. Prevention of neutrophil migration with colchicine may hold therapeutic potential in phosgene poisoning.
 ...
PMID:Reduction of neutrophil influx diminishes lung injury and mortality following phosgene inhalation. 165 61

Pseudomonas aeruginosa cytotoxin, a transmembrane pore-forming protein, causes an increase in pulmonary microvascular permeability with subsequent lung edema formation, possibly related to the induction of arachidonic acid (AA) lipoxygenase products. To investigate this, isolated rabbit lungs were perfused with cytotoxin-containing buffer (6.5 and 13 micrograms of toxin/ml). A severalfold increase in the capillary filtration coefficient was induced, both preceded and accompanied by a marked time- (15-60 min) and dose-dependent release of cysteinyl leukotrienes (LT), LTB4, and 5-, 12-, and 15-hydroxyeicosatetraenoic acids (HETEs) into the lung perfusate. In the bronchoalveolar lavage fluid, corresponding AA-derived products were detected; the total sum of HETEs surpassed that of cysteinyl LTs in this compartment. The lipoxygenase inhibitors AA861 (10 microM) and nordihydroguaiaretic acid (100 microM) and EGTA (5 mM) suppressed the intravascular and alveolar liberation of all 5-lipoxygenase-derived AA metabolites, paralleled by a marked reduction and retardation of microvascular permeability increase (AA861). It thus seems that Pseudomonas cytotoxin induces generation of LTs and HETEs in rabbit lungs that may contribute to the development of pulmonary microvascular injury evoked by this bacterial agent.
 ...
PMID:Induction of vascular injury by Pseudomonas aeruginosa cytotoxin in rabbit lungs is associated with the generation of different leukotrienes and hydroxyeicosatetraenoic acids. 189 1

We examined the effect of phospholipase A2 (PLA2; Naja naja) challenge on pulmonary hemodynamics, airway constriction, and fluid filtration in isolated Ringer-perfused guinea pig lungs. Intratracheal PLA2 (10-100 U) produced dose-dependent increases in pulmonary arterial pressure, intratracheal pressure, and lung weight, although intravenous PLA2 administration had no effect on monitored variables. Morphological features indicative of airway constriction and pulmonary edema were observed by light microscopy. PLA2-induced increases in intratracheal pressure and/or lung weight were attenuated to varying degrees by pretreatment with indomethacin (1 microM, a cyclooxygenase inhibitor), ICI-198,615 (1 microM, a leukotriene D4 receptor antagonist), and WEB 2086 (1 microM, a platelet-activating factor antagonist). PLA2-induced increases in pulmonary arterial pressure and intratracheal pressure were also reduced in lungs removed from animals pretreated with dexamethasone (50 mg/kg ip for 2 days; a steroidal antiinflammatory agent). Pyrilamine (1 microM, a histamine1-receptor antagonist) and Takeda AA861 (1 microM, a delta 5-lipoxygenase inhibitor) did not produce significant inhibitory effects on PLA2-induced pathophysiological changes. Intratracheal instillation of high-dose platelet-activating factor (50 micrograms) or lysophosphatidylcholine (100 micrograms) produced gradual increases in intratracheal pressure and lung weight, but these changes were not as large as those induced by PLA2. Thus these studies suggest that resident cell populations associated with airways may play an important role in PLA2-induced pathophysiological changes in the perfused guinea pig lung. These PLA2-induced effects are most likely partially mediated by generation of eicosanoids and platelet-activating factor.
 ...
PMID:Pulmonary responses to phospholipase A2 in the perfused guinea pig lung. 260 58

In the present study we have investigated the mechanisms of pulmonary edema caused by platelet-activating factor (PAF) in isolated rat lungs as well as in mice in vivo. In blood-free perfused and ventilated rat lungs, PAF increased lung weight by 0.59 +/- 0.18 g. The cyclooxygenase inhibitor aspirin (500 microM) blocked this response by one-third, and the quinolines quinine (330 microM), quinidine (100 microM), and chloroquine (100 microM) by two-thirds. Lipoxygenase inhibition (10 microM AA861) alone or in combination with thromboxane receptor antagonism (10 microM SQ29548) had no effect on PAF-induced weight gain. In combination with aspirin, quinine or quinidine completely prevented PAF-induced weight gain and the concomitant increase of the capillary filtration coefficient (K(f,c)). Pretreatment with quinine in vivo prevented not only PAF-, but also endotoxin-induced edema formation as assessed by Evans Blue extravasation. In addition, in vivo quinine prevented the endotoxin-induced release of tumor neurosis factor (TNF). Furthermore, in perfused lungs quinine reduced the PAF-induced increases in airway and vascular resistance, as well as thromboxane release. These findings demonstrate the following anti-inflammatory properties of quinolines: reduction of thromboxane and TNF formation; reduction of PAF-induced vasoconstriction and bronchoconstriction; and attenuation of PAF- and lipopolysaccharide (LPS)-induced edema formation. We conclude that the PAF- induced edema consists of two separate mechanisms, one dependent on an unknown cyclooxygenase metabolite, the other one sensitive to quinolines.
 ...
PMID:Quinolines attenuate PAF-induced pulmonary pressor responses and edema formation. 1055 49