Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A hyperdynamic sepsis model was set up in seven adult baboons to evaluate neutrophil-activating peptide-1/interleukin (IL)-8 (NAP-1/IL-8), IL-1 beta, IL-6, tumor necrosis factor-alpha (TNF alpha), and IFN-gamma in plasma. By continuous intravenous administration of 10(10) cfu/kg live Escherichia coli over 8 h with additional infusion therapy (less than or equal to 50 ml/kg/h), endotoxin plasma levels of 2.7-22.3 ng/ml were observed. In plasma the kinetics of NAP-1/IL-8 and IL-6 were similar to those of IL-1 at the end of the experiment (8 h) (peak median values, 34, 4197, and 230 ng/ml, respectively). Differences were greatest for IL-6. Monocyte activation during sepsis was confirmed by elevated plasma neopterin levels (91-139 mumol/mmol of creatine). Granulocyte activation was evident from both incipient neutropenia and the massive release of neutrophil elastase into the plasma as measured by a new immunoassay (peak level, 374 ng/ml). Thus, in primate bacteremia, early TNF release is followed by a concomitant increase of NAP-1/IL-8 with plasma kinetics similar to those of IL-6 and IL-1 and accompanied by massive activation of neutrophils.
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PMID:Plasma neutrophil-activating peptide-1/interleukin-8 and neutrophil elastase in a primate bacteremia model. 190 12

Cystic fibrosis (CF) is characterized by a dramatic neutrophil recruitment and repeated Pseudomonas infections in the lungs. To evaluate cytokine releasibility by airway epithelial cells in the context of CF, we studied primary nasal epithelial cells isolated from the upper airways and continuous epithelial cell lines from normal and CF subjects. Relatively low levels of interleukin (IL)-8, IL-6, and granulocyte/macrophage colony-stimulating factor (GM-CSF) were produced spontaneously by primary epithelial cells (< 50 pg/10(6) cells) and higher levels of colony-stimulating factor-1 (CSF-1) (1 to 2 ng/10(6) cells). Cells were stimulated with substances that are likely to be present in the inflamed lungs of CF patients-namely, the proinflammatory monokines IL-1 and tumor necrosis factor-alpha (TNF alpha) as well as neutrophil elastase and bacterial products from Pseudomonas (mucoid exopolysaccharide [MEP] and rhamnolipids). Both IL-1 and TNF alpha induced a dose-dependent release of IL-6 (5 to 10 ng/10(6) cells) and GM-CSF (2 to 3 ng/10(6) cells) by primary epithelial cells from eight normal volunteers. The TNF alpha/IL-1-stimulated GM-CSF release was blocked by the addition of 1 microM dexamethasone, whereas basal CSF-1 release was unaffected. Neutrophil elastase was a potent inducer of IL-8 and GM-CSF both in primary epithelial cells and in cell lines. Dexamethasone (1 microM) did not inhibit elastase-induced IL-8 release in either normal or CF epithelial cells. Rhamnolipids and MEP were found to stimulate the copious release of IL-8, GM-CSF, and IL-6 from epithelial cells, in a steroid-sensitive fashion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of interleukin-8, interleukin-6, and colony-stimulating factors by upper airway epithelial cells: implications for cystic fibrosis. 769 Nov 10

In juvenile rheumatoid arthritis (JRA), it is likely that the release of proteolytic enzymes from activated synovial fluid neutrophils overwhelms the major protease inhibitor, alpha 2-macroglobulin (alpha 2-MG), and leads to cartilage destruction. Due to the unique nature of the alpha 2-MG-protease complex, proteolytic function is maintained until the complex is cleared. In this study, we sought to determine the concentration of alpha 2-MG-protease complexes in synovial fluid of patients with JRA, the proteolytic activity found in their synovial fluid, and whether the alpha 2-MG complexes are associated with increased proteolytic activity. The JRA patients' synovial fluids had complex levels of 217.0 +/- 192.2 nmol/L--significantly elevated compared with plasma values (p < 0.001) and with control synovial fluid (p < 0.05). Elastase activity (almost entirely neutrophil elastase) was detected in all JRA synovial fluid samples (mean 2.9 +/- 2.6 mg/L) and significantly correlated with alpha 2-MG-complex values (r = 0.67, p < 0.01). Synovial fluid tryptic activity was detectable in all JRA patients but did not significantly correlate with alpha 2-MG complexes (r = 0.53, p > 0.05). Seventy-four percent of total elastase activity and 41% of total tryptic activity were contained in the alpha 2-MG-complex fractions. We suggest that the increased concentration of synovial fluid alpha 2-MG complexes with retained elastase activity contributes to continued proteolysis and joint destruction and may affect the subsequent disease course through its role as a modulator of IL-6.
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PMID:Intraarticular alpha 2-macroglobulin complexes and proteolytic activity in children with juvenile rheumatoid arthritis. 769 28

Chronic airway inflammation is an important feature of cystic fibrosis (CF), markedly influencing morbidity and mortality. We wanted to assess the contribution of the respiratory epithelium in the mediation of local inflammatory events, and, more particularly, its regulating role through cytokine secretion. We have studied the regulation of interleukin-6 and 8 (IL-6 and IL-8) production by the SV40 transformed airway epithelial cell line JME/CF15 (homozygous for the deletion of Phe 508). We show that unstimulated JME/CF15 cells secrete IL-6 and IL-8. Neutrophil chemotactic activity (NCA) is detected in supernatants. The secretion of IL-6 and IL-8 is increased following stimulation of the JME/CF15 cells by IL-1 beta and neutrophil elastase. Lipopolysaccharide and granulocyte macrophage colony stimulating factor (GM-CSF) have no effect on secretion of IL-6 or IL-8. Neutrophil elastase inactivates recombinant human IL-6 at 37 degrees C in vitro, but has no effect at 4 degrees C, suggesting a proteolytic effect of elastase on IL-6. IL-8 activity remains preserved, even after prolonged exposure to elastase. Our data suggest that the airway epithelium may play an active role in the mediation of neutrophil chemotaxis. Local production of IL-8 in response to elastase and IL-1 beta, together with the inactivation of the anti-inflammatory protein IL-6, may result in a significant upregulation of airway inflammation in cystic fibrosis.
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PMID:Regulation of cytokine secretion by cystic fibrosis airway epithelial cells. 811 34

The serum IL-6 and TNF alpha response to cardiopulmonary bypass surgery was studied in 12 patients. Human neutrophil elastase was also measured in order to detect the presence of neutrophil activation. Peripheral venous blood samples were obtained before, during, and 1, 2, 3 and 6 days after surgery. Intra-operative samples were also obtained from the coronary sinus and pulmonary artery. Cardiopulmonary bypass stimulated the immediate release of IL-6 into the coronary, pulmonary and systemic circulations. TNF alpha was transiently detected in the pulmonary circulation in seven patients. Surgery also induced early and sustained activation of neutrophils, which peaked 24 h following maximum IL-6 release. Both IL-6 and TNF alpha not only enhance neutrophil activation, but also stimulate an adhesive neutrophil-cardiac myocyte interaction which is associated with the release of toxic oxygen radicals. Their detection, in association with concomitant neutrophil activation, suggests a possible pathway for enhanced neutrophil mediated myocardial damage following cardiopulmonary bypass surgery.
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PMID:IL-6 and TNF alpha release in association with neutrophil activation after cardiopulmonary bypass surgery. 818 40

Myocardial ischaemia is one of the major causes of low output syndrome during open heart surgery. Injury associated with ischaemia and reperfusion has been considered to result, in part, from the action of neutrophils, the interaction of neutrophils with vascular endothelial cells, and the effects of cytokines which are mediators that induce and modify reactions between these substances. We investigated cell injury in relation to the concentrations of interleukins 6 and 8 (IL-6 and IL-8), which have recently received attention as neutrophil activators. Neutrophil counts, granulocyte elastase (GEL), IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha), CK, and CK-MB concentrations were determined serially in 11 patients undergoing open heart surgery with cardiopulmonary bypass (CPB). Neutrophil counts (mean +/- SD 2717 +/- 2421 microliters-1 preoperatively) peaked 60 min after declamping the aorta at 7432 +/- 4357 microliters-1 (P < 0.01) and remained elevated 7136 +/- 5194 microliters-1 at 180 min (P < 0.01). Plasma GEL level (168 +/- 71 micrograms.L-1 preoperatively) peaked at 1134 +/- 453 micrograms.L-1 120 min after declamping of the aorta (P < 0.01) and remained elevated, 1062 +/- 467 micrograms.L-1, after 180 min (P < 0.01). Serum IL-6 level (118 +/- 59 pg.ml-1 preoperatively) peaked at 436 +/- 143 pg.ml-1 60 min after declamping of the aorta (P < 0.01) and remained elevated, 332 +/- 109 pg.ml-1, after 180 min. Serum IL-8 level (37 +/- 44 pg.ml-1 preoperatively) peaked at 169 +/- 86 pg.ml-1 at 60 min after declamping of the aorta (P < 0.001) and remained elevated at 113 +/- 78 pg.ml-1 180 min after declamping of the aorta.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elevation of cytokines during open heart surgery with cardiopulmonary bypass: participation of interleukin 8 and 6 in reperfusion injury. 826 59

Multiple organ dysfunction syndrome (MODS) is a critical condition developing in the patients under overwhelming surgical insults such as a major surgery, severe trauma, extensive burn, and systemic sepsis. The host response to those surgical insults is the main pathogenetic factor contributing to the development of shock and MODS seen in surgical patients. The proinflammatory cytokines, TNF-alpha (TNF) and interleukin-1 beta (IL-1), are known to play a pivotal role in the pathogenetic mechanisms of MODS. In response to surgical insults, macrophages produce and release TNF and IL-1 which subsequently induce the production of other cytokines (IL-6, IL-8, etc.) and other endogenous chemical mediators (growth factors, adhesion molecules, complement cleavage products, thrombin, eicosanoids, PAF, nitric oxides, oxygen-free radicals, granulocyte elastase, etc.) The resultant systemic inflammation may develop into shock and MODS when the primary insults are overwhelming (early MODS) or a second inflammatory insult such as sepsis triggers an exaggerated inflammation. In the patients suffering from MODS, a systemic release of various cytokines is not properly regulated, and the high blood levels of the proinflammatory cytokines induce an autodestructive generalized inflammatory reaction. This condition is termed "Cytokine Storm" by the author. In the cytokine storm, not only proinflammatory cytokines but also anti-inflammatory cytokines are elevated in the blood stream. With the recent understanding of the biological and pathological roles of cytokines and other mediators, a new therapeutic strategy has been developed. In addition to the reduction of the surgical insults, a variety of anti-cytokine therapy and anti-mediator therapy has been tested in an attempt to prevent or treat the life-threatening MODS.
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PMID:[Cytokine storm in the pathogenesis of multiple organ dysfunction syndrome associated with surgical insults]. 894 Jun 90

Infectious complications are the leading cause of death in acute pancreatitis. Individual factors of immune defence could be of significance, whether or not a patient develops a severe course with infectious complications. In a prospective 5-year trial including 72 patients, we investigated 29 cellular and humoral markers of the body's defence system for their potential to indicate the severity and course of acute pancreatitis. Complement factors C3 and C4 as well as immunoglobulins IgG, IgM and IgA were normal, in general. Measurable levels of IL-1 alpha, IL-1 beta, IL-2 and sIL-2R could be detected only occasionally. Values of alpha 1-AT, TNF-alpha, TNF alpha-Rp75, neopterin, sICAM-1, IL-8, IL-1RA and sIL-6R did not correlate with a severe course. Due to the high magnitude of increase, CRP, IL-6 and granulocyte elastase were the best indicators of the inflammatory process. Delayed-type hypersensitivity response was the only early predictor of a severe course. It was superior over other cellular markers such as monocyte count or CD4+/CD8+ ratio. In vitro function of polymorphonuclear granulocytes (PMN) was not adequate to the severity of the disease already during the first week of illness. During further course, PMN motility and capacities to produce reactive oxygen species even worsened. The compromized PMN function could explain the frequent development of infectious complications in patients suffering from severe pancreatitis. These results should encourage new concepts of infection prophylaxis using stimulants of cellular defence.
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PMID:[Cellular and humoral functions in acute pancreatitis]. 913

Thoracoscopy is useful for diagnosis of a number of lung diseases. We report our recent experience with thoracoscopy in 86 patients and with video-assisted thoracic surgery in 105 patients. In 70 patients with pleural effusion, thoracoscopic pleural biopsy was done under local anesthesia. All malignant pleural effusions that were not diagnosed by cytologic examination of pleural effusion fluid were diagnosed by thoracoscopy. Especially in malignant mesothelioma, thoracoscopy yielded correct diagnoses. No complication was observed. In 45 patients with a solitary pulmonary nodular lesion and in 27 patients with diffuse interstitial lung diseases, thoracoscopic lung biopsy was done with an "endo-stapler", under general anesthesia. The diagnostic accuracy of this procedure was excellent. Plasma neutrophil elastase and IL-6 levels were measured after surgery as markers of the invasiveness of the procedure. The results indicated that thoracoscopic lung biopsy is relatively safe and non-invasive. Thoracoscopy has become an indispensable tool in the daily practice of pulmonology.
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PMID:[Utility of thoracoscopy for diagnosis of pulmonary diseases in clinical pulmonary medicine]. 921 7

This study investigates in vitro effects of specific neutrophil elastase inhibitor ONO-5046.Na on production of proinflammatory cytokines by human monocytes in a neutrophil-free system. Isolated human monocytes were cultured with lipopolysaccharide in the presence or absence of ONO-5046.Na. The production of proinflammatory cytokines was assessed by the measurement of cytokine level in the culture supernatant. ONO-5046.Na significantly inhibited the production of IL-1 beta and IL-6 at the doses between 10(-9) and 10(-7) M, and TNF-alpha at the doses between 10(-9) and 10(-4) M. These results suggest that ONO-5046.Na at clinically available concentrations can inhibit the cytokine production by monocytes. This drug could act as a dual inhibitor of neutrophils and monocytes in inflammatory tissue destruction.
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PMID:Neutrophil elastase inhibitor (ONO-5046.Na) decreases production of proinflammatory cytokines by lipopolysaccharide-stimulated human monocytes. 948 18


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