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

Although active transport of ions could play an important role in the resolution process of pulmonary edema, the exact mechanism regulating this process is still unknown. In this study, we investigated the effect of phorbol myristate acetate (PMA) on lung liquid clearance in anesthetized, ventilated sheep to evaluate the possible role of protein kinase C. To study lung liquid and protein clearance, we measured the removal of 100 ml of autologous serum from the air spaces of anesthetized sheep. Either serum alone or serum mixed with PMA (10(-7) M) was instilled. After 4 h, the residual lung water was 76.8 +/- 9.2 ml when serum alone was instilled and 79.5 +/- 15.7 when serum with PMA (10(-7) M) was instilled. The lack of effect of PMA (10(-7) M) on lung liquid clearance cannot be explained by increased movement of liquid from the vascular space to the air space since we did not have any evidence of increased pressure or increased permeability in the lung. This lack of effect of PMA (10(-7) M) is not due to an absence of stimulation of protein kinase C since instillation of BSA and PMA (10(-7) M) in rat lung produced a translocation of protein kinase C activity from the cytosolic fraction to the membrane fraction 2 h after the instillation. These results were confirmed in two sheep experiments, which demonstrated clear activation of protein kinase C after 4 h. These data suggest that activation of protein kinase C does not stimulate lung liquid clearance. However, a possible role of protein kinase C in modulating lung liquid clearance has not been excluded.
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PMID:Protein kinase C activation does not stimulate lung liquid clearance in anesthetized sheep. 195 36

We investigated the effect of dioctanoylglycerol (DOG), a second messenger of protein kinase C (PKC) activation, in the absence and presence of neutrophils in isolated perfused guinea pig lung. DOG was given after a base-line isogravimetric steady-state period. Pulmonary capillary pressure (Ppc) and change in lung weight (delta W) were monitored at 15, 30, and 60 min. Capillary filtration coefficient (Kf,c, an index of vascular permeability) was measured during base-line period and at 30 min. DOG increased the Ppc and delta W at 30 and 60 min, and the Kfc at 30 min. Monooctanoylglycerol, a monoacylglycerol that does not activate PKC, had no effect on Ppc, Kf,c, and delta W. Pretreatment with two different PKC inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methyl piperazine or staurosporin, prevented the pulmonary response to DOG. With neutrophils present, DOG caused greater increases in delta W and the (wet-dry)-to-dry wt ratio compared with DOG group. Response to DOG+ neutrophils was due to oxygen radical production because it was prevented by pretreatment with catalase and because DOG increased superoxide release from neutrophils. PKC activation using DOG in the isolated lung results in pulmonary edema mediated by increases in capillary pressure and vascular permeability. Lung weight-gain response to DOG is greater in the presence of neutrophils. Response to DOG+ neutrophils is mediated by oxygen radicals.
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PMID:Mechanisms of pulmonary edema induced by a diacylglycerol second messenger. 215 34

In rabbits intravenous administration of antibodies to lung angiotensin converting enzyme (ACE) results in a rapid redistribution of ACE on the plasma membrane of pulmonary endothelium with fixation of complement and development of fatal pulmonary edema. In survivors given daily injections of antibodies, ACE disappears from the lung ("antigenic modulation") and the rabbits become resistant to further immune injury. To test the hypothesis that these events depend on a functionally intact mechanism of cell activation, rabbits received, in addition to anti-ACE antibodies, chlorpromazine, a drug that inhibits calmodulin and protein kinase C and decreases plasma membrane fluidity. Initially, chlorpromazine inhibited antigen redistribution, fixation of complement, and development of pulmonary edema. In rabbits maintained on chlorpromazine and receiving daily anti-ACE antibodies this effect became attenuated and the rabbits eventually developed ACE redistribution, complement fixation, and pulmonary edema. We conclude that chlorpromazine temporarily inhibits antigenic modulation in vivo, presumably through its action on calcium-mediated antibody-cell surface antigen interaction.
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PMID:Lung injury mediated by antibodies to endothelium. III. Effect of chlorpromazine in rabbits. 217 23

We investigated the effect of H2O2 (92 microM) in isolated guinea pig lungs perfused with a buffered Ringer solution. Pulmonary arterial pressure (Ppa), pulmonary capillary pressure (Ppc), and change in lung weight (delta W) were recorded at 0 min and at 15, 30, and 60 min after the H2O2. The capillary filtration coefficient (Kfc) was measured at 0 and 30 min. The perfusion of H2O2 increased the Ppa, Ppc, delta W, and Kfc. The thromboxane synthetase inhibitor Dazoxiben, or the vasodilator papaverine, prevented the increases in Ppa and Ppc. The protein kinase C (PKC) inhibitor H7 [1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride] prevented the increases in Ppa, Ppc, delta W, and Kfc, whereas the inactive isoquinoline HA1004 [N-(2-guanidinoethyl)-5-isoquinolinesulfonamide hydrochloride] had little effect on the H2O2 response. H2O2 increased the number of stress fibers and disrupted the peripheral band of cultured confluent endothelial cells, changes that were prevented with pretreatment with H7. PKC may mediate the increases in vascular permeability and pulmonary edema that occur in response to H2O2.
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PMID:Protein kinase inhibitor prevents pulmonary edema in response to H2O2. 270 44

The effect of the protein kinase C enzyme inhibitor H-7 on the noncardiogenic lung edema induced by phorbol myristate acetate (PMA) in mice was examined. Lung edema was assessed by measurement of 125I-labeled albumin leak into the lung. The results showed that pretreatment of mice with H-7 nearly prevents the albumin leak induced by PMA, whereas post-PMA treatment with H-7 had less of an effect on the albumin leak, although it was still significant.
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PMID:Inhibition of induced acute lung edema by a novel protein kinase C inhibitor. 360 9

Complement-mediated pulmonary edema results from increases in lung capillary hydraulic conductivity (Lp), possibly by receptor-mediated mechanisms. We considered the Lp effects of vitronectin and the vitronectin-containing complement complex SC5b-9, which ligate the integrin alpha v beta 3. Vitronectin, SC5b-9, and SC5b-9-enriched zymosan-activated serum all rapidly increased Lp, as determined by the split-drop technique in single lung capillaries of rat lung. The Lp increases were inhibited by a monospecific (LM609) and a polyclonal (R838) antibody against the alpha v beta 3 integrin but not by an irrelevant monoclonal antibody isotype matched with LM609, by a monoclonal antibody against the alpha v beta 5 integrin, or by preimmune rabbit serum. Vitronectin monomers failed to increase Lp. The tyrosine kinase blockers genistein and methyl 2,5-dihydroxycinnamate caused significant concentration-dependent inhibitions of Lp increases due to vitronectin and zymosan-activated serum. By contrast, the protein kinase C blocker calphostin C had no major effect. We conclude that (1) multivalent ligation of the luminally located alpha v beta 3 integrin of lung capillary endothelium increases transcapillary liquid flux, and (2) the dominant signal transduction pathway for this effect occurs through tyrosine kinase activation.
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PMID:Ligation of endothelial alpha v beta 3 integrin increases capillary hydraulic conductivity of rat lung. 755 9

Fusarium moniliforme (FM) is a major fungal pathogen of corn and is involved with stalk rot disease. FM is widely spread throughout the world, including the United States. Most strains of FM produce several mycotoxins, the most prominent of which is called fumonisin. Recent epidemiological studies indicated that ingestion of fumonisin correlates with a higher incidence of esophageal cancer in Southern and Northern Africa and China. Furthermore, fumonisin causes a neurodegenerative disease in horses, induces hepatic cancer in rats, and induces pulmonary edema in swine. Considering that high levels of fumonisin have been detected in healthy and diseased corn grown in the United States, fumonisin may pose a health threat to humans and livestock animals. Structurally, fumonisin resembles sphingolipids which are present in the membranes of animal and plant cells. At the present time, very little is known concerning the mechanism by which fumonisin elicits its carcinogenic effect. Our studies indicate that fumonisin represses expression of protein kinase C and AP-1-dependent transcription. In contrast, fumonisin stimulated a simple promoter containing a single cyclic AMP response element. Since fumonisin did not alter protein kinase A activity, it appears that cyclic AMP response element activation was independent of protein kinase A. It is hypothesized that the ability of fumonisin to alter signal transduction pathways plays a role in carcinogenesis.
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PMID:Repression of protein kinase C and stimulation of cyclic AMP response elements by fumonisin, a fungal encoded toxin which is a carcinogen. 771 70

Although active transport of sodium plays an important role in the resolution of pulmonary edema, the biochemical regulation of this process is still under investigation. The purpose of this study was to evaluate the activity of protein kinase C during the process of lung liquid clearance. Alveolar flooding was induced by instilling 5% bovine serum albumin solution, saline, or heterologous serum in the air spaces of rats. The activity of protein kinase C was measured in both the instilled and control lungs at 10 min and 1 and 4 h after fluid instillation. Four hours after instillation of 5% bovine serum albumin, the ratio of protein kinase C activity in the instilled lung compared with the control lung was 2.2 +/- 0.3. Similar results were obtained following instillation with heterologous serum or saline. Since we measured a clearance rate of 0.8 ml/h in anesthetized rats, we can postulate that the activation of protein kinase C occurred when > 40% of the liquid had been cleared from the lung. This increased activity of protein kinase C was not due to an increase in kinase activity in the inflammatory cells or an increase in enzyme quantity but due to a decrease of protein kinase C inhibitory activity in the lung. These results suggest that protein kinase C second messenger system may play a regulatory role in lung liquid clearance.
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PMID:Protein kinase C activity during the process of lung liquid clearance. 833 83

The present study determined the effects of cotton smoke inhalation on the functioning of alveolar macrophages (mphi). Smoke inhalation led to dose-dependent impairment of respiratory gas exchange by 48 h postexposure and pulmonary edema by 96 h. Maximal effects were observed in animals ventilated with 54 breaths of cotton smoke (3-min exposure, 18 breaths/min). Macrophages were obtained at 48 h postexposure by bronchoalveolar lavage of rabbits subjected to 54 breaths of smoke or room air (control). Phagocytosis of opsonized bacteria and adherence to solid substratum were reduced in smoke-exposed mphi. Smoke inhalation primed mphi for release of tumor necrosis factor-alpha (TNF-alpha) induced by lipopolysaccharide (LPS). Smoke-exposed mphi were also primed for TNF-alpha release induced by phorbol myristate acetate, which suggests that the priming event occurred downstream of protein kinase C activation in the signal transduction pathway. Further, smoke exposure attenuated the inhibitory effects of phosphodiesterase inhibitors on LPS-induced TNF-alpha release. Thus, the priming event may be mediated through cAMP and/or protein kinase A. The data indicate that cotton smoke inhalation suppresses the antimicrobial activities of alveolar mphi and can lead to excessive mphi production of TNF-alpha. These mphi effects would be expected to contribute to the pathophysiological abnormalities associated with smoke inhalation injury.
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PMID:Cotton smoke inhalation primes alveolar macrophages for tumor necrosis factor-alpha production and suppresses macrophage antimicrobial activities. 968 28

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.
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PMID:Pertussis toxin-induced lung edema. Role of manganese superoxide dismutase and protein kinase C. 1003 Aug 45


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