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)

(TNF alpha)-induced sequestration of neutrophils (PMN) in lungs and of the resultant PMN-dependent pulmonary edema. Guinea pig lungs perfused with Ringers-albumin were challenged with TNF alpha (1,000 U/ml) for 90 min, followed by addition of fresh perfusate containing 2 x 10(7) human PMN. TNF alpha challenge caused sequestration of PMN in the pulmonary vascular bed as indicated by a threefold increase in lung tissue myeloperoxidase activity (MPO). The activation of the sequestered PMN with phorbol 12-myristate 13-acetate (PMA; 5 x 10(-9) M) produced threefold increases in pulmonary artery (Ppa) and pulmonary capillary hydrostatic (Pcap) pressures, and twofold increases in lung wet-to-dry weight (W/D) ratio and capillary filtration coefficient (Kf,c) over baseline. TNF alpha prestimulation was required for these responses since activation of PMN with PMA in control lungs produced smaller increases in Ppa and Pcap (P less than 0.01) and did not change the W/D and Kf,c. TNF alpha prestimulation also induced the expression of intercellular adhesion molecule (ICAM-1) on pulmonary vascular endothelial cells. Monoclonal antibodies (mAbs) to the neutrophil CD18 integrin (beta-chain of CD11/CD18 complex) (mAb IB4) and to its endothelial cell ligand ICAM-1 (mAb RR1/1) were used to examine the role of PMN adhesion in the TNF alpha-induced responses. Pretreatment of PMN with mAb IB4 prevented PMN uptake and increases in Ppa, Pcap, Kf,c, and W/D ratio. Addition of mAb RR1/1 to the perfusate reduced PMN uptake by 58%, and prevented the increases in Ppa, Pcap, Kf,c, and W/D ratio, as with mAb IB4. The findings indicate that TNF alpha prestimulation of lungs mediates PMN uptake and that this requires the expression of ICAM-1 and its interaction with CD18 integrin on PMN. The activation of PMN sequestered by ICAM-1-dependent mechanism contributes to the development of pulmonary vascular injury and edema.
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PMID:Tumor necrosis factor mediates experimental pulmonary edema by ICAM-1 and CD18-dependent mechanisms. 134 98

We examined the role of intracellular adhesion molecule 1 (ICAM-1 or CD54) in the development of pulmonary edema in rabbits after pulmonary artery occlusion and reperfusion using a monoclonal antibody (MAb) RR1/1 directed against ICAM-1, a ligand for the CD18 leukocyte adhesion glycoprotein complex. A vascular clamp was placed around the left pulmonary artery for 24 h and then released to allow reperfusion for 2 h. Lungs subjected to 24 h of unilateral pulmonary artery occlusion showed increased binding of 125I-labeled RR1/1 and immunocytochemical evidence of ICAM-1 expression in pulmonary vascular endothelial cells compared with the contralateral lung. MAbs RR1/1 (0.5 mg/kg) or IB4 (1.0 mg/kg) (MAb directed against an epitope on the CD18 adhesion glycoprotein) was infused 45-60 min before the start of reperfusion to assess the roles of ICAM-1 and CD18 in the response. After reperfusion, the lungs were removed, suspended from one end of a weighing balance, and perfused with Ringer-albumin (0.5 g/100 ml), and the changes in lung weight were monitored for 60 min. Lung tissue myeloperoxidase (MPO) content (a marker of neutrophil sequestration) was determined after reperfusion. The increases in lung weight gain in the RR1/1- and IB4-treated groups of 960 +/- 100 and 865 +/- 110 mg, respectively, were less (P less than 0.05) than in untreated controls (3,550 +/- 725 mg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of ICAM-1 in neutrophil-mediated lung vascular injury after occlusion and reperfusion. 168 73

Neutrophil inhibitory factor (NIF) is a recently cloned 41-kDa protein from the canine hookworm that binds CD11b/CD18 and inhibits CD11b/CD18-dependent neutrophil adhesion. We evaluated NIF's effects on neutrophil-dependent lung injury in guinea pigs. Pulmonary vascular endothelial CD54 (ICAM-1) was induced in buffer-perfused lungs by 90-min exposure to 1000 U/ml TNF-alpha. Human neutrophils (2 x 10(7)) were added to the perfusate and activated by 5 x 10(-9) PMA; in some lungs, the neutrophils were pretreated with NIF (100 nM) before their addition to the perfusate. Lung injury was assessed by wet:dry weight ratio, and neutrophil uptake by lung myeloperoxidase (MPO) activity. HUVEC exposed to TNF-alpha for 90 min were assayed for neutrophil adhesion, and we compared PMA-stimulated neutrophil adhesion to endothelial cells and fibrinogen-coated plates. PMA-induced pulmonary edema (lung wet:dry ratio increased from 8.8 +/- 0.7 to 18.8 +/- 4.4) was inhibited by NIF (10.0 +/- 1.0). Lung MPO activity concomitantly decreased from 17.1 +/- 6.1 to 8.7 +/- 1.8 U/mg dry lung tissue in the NIF-treated group, similar to controls (6.9 +/- 2.0). Endothelial monolayer experiments confirmed that NIF reduced neutrophil adherence (basal adhesion of 11 +/- 3% increased to 30 +/- 5% with TNF-alpha pretreatment of endothelial cells, an increase that was reduced to 10 +/- 4% with NIF). Moreover, NIF prevented PMA-induced neutrophil adhesion to fibrinogen, a CD11b/CD18-dependent event, but produced a smaller decrease in adherence to endothelial cells, which also involves CD11a/CD18 integrins. These studies indicate that NIF prevents neutrophil-dependent lung vascular injury by inhibiting neutrophil adhesion to the TNF-alpha-activated endothelium.
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PMID:Neutrophil inhibitory factor prevents neutrophil-dependent lung injury. 759 91

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)
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PMID:Increases in lung tissue expression of intercellular adhesion molecule-1 are associated with hyperoxic lung injury and inflammation in mice. 810 35

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.
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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

Lung injury is a major cause of patient morbidity in acute pancreatitis. The purpose of this study was to examine the mechanism of pulmonary infiltration and lung injury in acute pancreatitis. Mice were fed a choline-deficient/ethionine-supplemented (CDE) diet for 144 hours to induce severe acute pancreatitis. Serum samples were collected for measurement of biochemical markers of disease and for the detection of tumor necrosis factor-alpha (TNF-alpha). Cell surface adhesion molecule expression was quantified by the sensitive radiolabeled dual monoclonal antibody technique. Neutrophil sequestration in lung tissue was measured by the myeloperoxidase assay. Lung injury was determined histologically and lung edema was assessed by wet/dry ratios. Pancreatic injury was demonstrated to occur in all CDE-fed mice, which developed significant hyperamylasemia and hypoglycemia by 48 hours (P <0.0001). Serum TNF-alpha levels increased significantly by 48 hours over baseline values (P <0.02). Expression of intracellular adhesion molecule (ICAM-1) in pulmonary endothelia was significantly increased above baseline by 30% at 48 hours (P <0.02) and peaked at 120 hours by 100% (P <0.0001). Vascular cellular adhesion molecule (VCAM-1) was constitutively expressed at baseline and was upregulated threefold by 48 hours (P <0.0001). Neutrophil infiltration increased gradually 24 hours after ICAM-1 and VCAM-1 were upregulated with significant elevation of myeloperoxidase activity over baseline at 72 hours (7.2 +/- 1.2 vs. 18.1 +/- 2.2 activity units/gram tissue; P <0.05). Neutrophil infiltration peaked at 144 hours (26.24 +/- 10.49 activity units/gram tissue P <0.0001), and its kinetics correlated with the onset and progression of morphologic injury as well as increased lung edema. These results show that acute pancreatitis is associated with a systemic release of inflammatory cytokines, followed by increased expression of pulmonary ICAM-1 and VCAM-1, neutrophil infiltration, and histologic lung injury. The adhesion molecule axis may be a potential target for practical intervention to ameliorate lung injury and morbidity in acute pancreatitis.
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PMID:Temporal correlation of tumor necrosis factor-alpha release, upregulation of pulmonary ICAM-1 and VCAM-1, neutrophil sequestration, and lung injury in diet-induced pancreatitis. 1076 87

Hemorrhagic shock (HS) elicits an inflammatory response characterized by increased cytokine production and recruitment of PMN which we previously found to be iNOS dependent. In this study we attempted to remove excess induced-NO by administration of the NO scavenger, NOX, with the goal of suppressing proinflammatory signaling and reducing organ damage. Rats subjected to HS (MAP = 40 mmHg for 100 min) followed by resuscitation and examined 24 h later demonstrated histological signs of lung injury including pulmonary edema as well as an 8.6-fold increase in MPO-positive PMN. These events were accompanied by a 3.9-fold increase in mRNA levels for IL-6, 3.7-fold for ICAM-1, 3.5-fold for IL-1beta, and 7.3-fold for TNFalpha compared to sham animals. Immunostaining of the lungs of shock animals demonstrated IL-6 protein localized to cells lining the luminal sides of bronchiols. These animals also demonstrated a 2-fold and 5.5-fold increase in activation of NF-kappaB and Stat3 (an IL-6 signaling intermediate), respectively. Administration of NOX (30 mg/kg/h beginning at 60 min of shock for total of 4.5 h) resulted in reduced lung injury as measured by a 46% reduction in PMN infiltration, a 20% decrease in wet-to-dry ratio, and improved arterial blood gases. NOX reduced proinflammatory signaling in the lung as demonstrated by a 62% decrease in NF-kappaB binding, 47% reduction in Stat3 binding, a reduction in mRNA expression of 48% for IL-6, 57% for ICAM-1, 67% for IL-1beta, and 64% for TNFalpha, as well as a marked reduction in the intensity of IL-6 protein staining. These data indicate that NOX prevents lung injury in this HS model, possibly through downmodulation of proinflammatory signaling and the shock-induced inflammatory response.
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PMID:A nitric oxide scavenger protects against pulmonary inflammation following hemorrhagic shock. 1183 96

All-trans retinoic acid (ATRA) induces complete remission in patients with acute promyelocytic leukemia (APL). However, ATRA sometimes causes retinoic acid syndrome (RAS) characterized by respiratory distress, pleural effusions, fever and weight gain. To investigate the pathophysiology of RAS, we generated an animal model by injecting an APL cell line, NB4, into immunodeficient mice. When NOD/scid mice were injected intravenously with fully differentiated NB4 cells (1 x 10(7)) and then given a daily administration of ATRA, three of 12 mice died of pulmonary edema within 14 days. Pathologically, dilated lung capillary vessels and alveolar effusions were observed. After the injection, NB4 cells were detected in the lung within 2 days and in the pleural effusion later on. The gene expression levels of CXC chemokines (MIP-2 and KC) and ICAM-1 were increased in the lung and heart by the ATRA administration. In immunohistochemical analyses, MIP-2 was clearly detected in alveolar macrophages of the lung in mice with RAS. Dexamethasone treatment prevented the development of RAS and decreased the CXC chemokine mRNA expression in the lung. These findings suggested that the activation of adhesion molecules for leukocytes and expression of CXC chemokines in the lung are closely involved in triggering RAS.
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PMID:Retinoic acid syndrome in NOD/scid mice induced by injecting an acute promyelocytic leukemia cell line. 1474 6

In this study, the potential anti-inflammatory effect of San-Huang-Xie-Xin-Tang (SHXT) and its main component baicalin on LPS-induced lung injury were investigated and compared to the profile of dexamethasone (DEXA) in a pre-clinical animal model. Post-treatment with SHXT (75 mg/kg), baicalin (1.5 mg/kg) and DEXA (0.5 mg/kg), significantly inhibited LPS-induced hypotension, lung edema and acute survival rates. Western blotting analysis results indicated that all of them significantly inhibited LPS-induced iNOS, TGF-beta, p38MAPK, and ICAM-1 expressions in the lung tissues. Results from ELISA analysis showed that SHXT, baicalin and DEXA all decreased plasma levels of IL-1beta, TNF-alpha, and MCP-1 caused by LPS. Based on these findings, SHXT and baicalin decreased plasma concentrations of IL-1beta, TNF-alpha, MCP-1, and expressions of TGF-beta, ICAM-1, phosphorylated p38 MAPK, and iNOS, which were associated with lung injury and lethality. These evidences indicated that SHXT and baicalin showed strong anti-inflammatory activity, similar to that observed for DEXA, and therefore implicated that herbal SHXT might be therapeutically useful for the treatment of endotoxic lung injury.
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PMID:San-Huang-Xie-Xin-Tang attenuates inflammatory responses in lipopolysaccharide-exposed rat lungs. 1587 12

Hemorrhagic shock followed by resuscitation (HSR) causes neutrophil sequestration in the lung which leads to acute lung injury (ALI). Neutrophil elastase (NE) is thought to play a pivotal role in the pathogenesis of ALI. This study investigated whether sivelestat, a specific NE inhibitor, can attenuate ALI induced by HSR in rats. Male Sprague-Dawley rats were subjected to hemorrhagic shock by withdrawing blood so as to maintain a mean arterial blood pressure of 30+/-5 mm Hg for 60 min followed by resuscitation with the shed blood. HSR-treated animals received a bolus injection of sivelestat (10 mg/kg) intravenously at the start of resuscitation followed by continuous infusion for 60 min (10 mg/kg/h) during the resuscitation phase, or the vehicle. Lung injury was assessed by pulmonary histology, lung wet-weight to dry-weight (W/D) ratio, myeloperoxidase (MPO) activity, gene expression of tumor necrosis factor (TNF)-alpha and inducible nitric oxide synthase (iNOS), DNA binding activity of nuclear factor (NF)-kappaB, and immunohistochemical analysis of intercellular adhesion molecule (ICAM)-1. HSR treatment induced lung injury, as demonstrated by pulmonary edema with infiltration of neutrophils, the increase in lung W/D ratio, MPO activity, gene expression of TNF-alpha and iNOS, and DNA-binding activity of NF-kappaB, and enhanced expression of ICAM-1. In contrast, sivelestat treatment significantly ameliorated the HSR-induced lung injury, as judged by the marked improvement in all these indices. These results indicate that sivelestat attenuated HSR-induced lung injury at least in part through an inhibition of the inflammatory signaling pathway, in addition to the direct inhibitory effect on NE.
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PMID:A neutrophil elastase inhibitor, sivelestat, ameliorates lung injury after hemorrhagic shock in rats. 1720 97


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