Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human neutrophil elastase plays an important role in the development of several inflammatory lung diseases; however, there have been relatively few investigations using plasma samples. In this report, we describe alterations in the plasma elastase:alpha 1-PI complex in patients with chronic obstructive pulmonary disease (COPD) (15 cases), COPD with infection (8), diffuse panbronchiolitis (DPB) (8), bronchiectasis (9), pneumonia (10), and the adult respiratory distress syndrome (ARDS) (14), and in 15 normal volunteers. The elastase:alpha 1-PI complex concentration was determined by an enzyme-linked immunosorbent assay. Western immunoblot analysis of the elastase:alpha 1-PI complex was also performed. Plasma elastase:alpha 1-PI complex was also performed. Plasma elastase:alpha 1-PI complex levels in patients with COPD with infection (504 micrograms/L +/- 93 micrograms/L) were significantly higher, as compared with those with COPD but without infection (118 micrograms/L +/- 9 micrograms/L) and normal volunteers (122 micrograms/L +/- 4 micrograms/L). Increased complex concentrations were also found in patients with DPB and bronchiectasis (643 micrograms/L +/- 222 micrograms/L and 558 micrograms/L +/- 198 micrograms/L, respectively) as compared with normal volunteers. Increased complex concentrations were also found in patients with pneumonia and ARDS (450 micrograms/L +/- 101 micrograms/L and 1,400 micrograms/L +/- 438 micrograms/L, respectively). Western immunoblot analysis using anti-alpha 1-PI antibody and antineutrophil elastase antibody showed two types of elastase:alpha 1-PI complexes, one with a molecular weight of 60,000 daltons (60 kilodaltons [KD]) and the other at 50,000 daltons (50 KD). Although the native 80-KD elastase:alpha 1-PI complex was detected in bronchoalveolar lavage fluid, it was not found in plasma. In summary, these results demonstrated that levels of the truncated complex were increased in patients with various inflammatory lung diseases. This truncated form may play an important role in the pathophysiology of inflammatory processes.
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PMID:Elevation of plasma truncated elastase alpha 1-proteinase inhibitor complexes in patients with inflammatory lung diseases. 162 39

During staphylococcal pneumonia massive destruction of lung tissue is often observed. Staphylococcal serine proteinase (SSP) inactivates alpha-1-proteinase inhibitor (alpha 1PI) a major factor which protects lungs from phagocyte proteases. We investigated the effect of SSP on elastin degradation by porcine pancreatic elastase (PE) and crude extract of human neutrophil elastase (NE) in solution and gel containing alpha 1PI. SSP having no elastase activity enhanced PE and NE-induced elastinolysis in solution when added to alpha 1PI before mixing with elastase and then with elastin. SSP added simultaneously with alpha 1PI to PE had no influence on elastin degradation. However, SSP added simultaneously, 30 min before or 30 min after PE significantly increased elastin digestion in elastin-agarose plate with alpha 1PI. Maximal increase in elastinolysis about 3-fold was for SSP added 30 min prior to PE. Since elastin is the major component of the alveolar walls it is possible that lung damage in the course of staphylococcal infection may partly depend on action of SSP.
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PMID:Serine proteinase from Staphylococcus aureus enhances elastin degradation by elastases in the presence of human alpha-1-proteinase inhibitor. 185 84

To test whether neutrophils infiltrate and degranulate in areas of chronic respiratory allergic inflammation, we developed an indirect immunofluorescence technique to localize neutrophil elastase in formalin-fixed, paraffin-embedded tissues. The affinity-purified antielastase stained only neutrophils on peripheral blood buffy coat smears, and in lung tissue from patients with pneumonia. We examined tissue specimens from four patients with fatal asthma, 10 patients with chronic sinusitis, and 10 patients with nasal polyposis for the presence of elastase, as well as eosinophil granule major basic protein (MBP). Neutrophil infiltration and extracellular elastase deposition in association with damage to respiratory epithelium were generally sparse in most specimens; the exceptions were one patient with asthma, one patient with chronic sinusitis, and two patients with nasal polyposis. In contrast, eosinophil infiltration and extracellular MBP deposition were generally marked in most specimens; the exceptions were one patient with asthma and one patient with nasal polyps where extracellular MBP deposition did not coincide with damage to respiratory epithelium. The results suggest that the neutrophil does not usually infiltrate tissues showing allergic inflammation; however, on occasion, it may participate in these inflammatory reactions.
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PMID:The neutrophil and chronic allergic inflammation. Immunochemical localization of neutrophil elastase. 217 30

We previously demonstrated that pneumococcal extracts contain a highly specific inhibitor of human neutrophil elastase (HNE). We now show that the active inhibitor in these extracts is a high-molecular-weight, heat-stable substance that appears to be RNA, since inhibitory activity of pneumococcal extracts is decreased by incubation with ribonuclease but not by incubation with deoxyribonuclease or proteinase K. Moreover, metabolically labeled ([3H]uridine) pneumococcal RNA, isolated by phenol extraction followed by ethanol precipitation, strongly inhibits HNE. Pneumococcal capsular polysaccharide, although polyanionic, is only weakly inhibitory toward HNE and is not a major source of elastase-inhibitory activity in pneumococcal extracts. On the other hand, the capsule of Haemophilus influenzae type b contains polyribosylribitol phosphate. This highly charged polyanion possesses HNE-inhibitory activity, but only under special circumstances to be discussed below. Pneumococci (type I, type II smooth, type II rough) and H. influenzae (type b) all release HNE-inhibitory activity into their culture medium during growth. By contrast, Klebsiella pneumoniae and Staphylococcus aureus release little (if any) stable HNE-inhibitory activity during growth. We propose that some bacterial pneumonias may spare host tissue because polyanions released by the invading microorganisms (e.g. RNA from autolysing pneumococci) inhibit elastase released from inflammatory neutrophils and thereby modulate accompanying tissue proteolysis. Pneumonias caused by microorganisms that do not release stable polyanionic inhibitors of HNE (e.g., Staphylococcus and Klebsiella) may be correspondingly more injurious to the lung.
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PMID:Inhibition of human neutrophil elastase by bacterial polyanions. 244 47

A neutrophil elastase-inhibitor isolated from lysed pneumococcal cells, as well as trypsin-digest peptides derived from this factor, were tested for their ability to suppress acute lung injury in mice treated with human neutrophil granule extracts. Injury was assessed by measuring pulmonary sequestration of circulating 125I-labeled albumin, lung water, and lung hemoglobin. Both the native inhibitor and the tryptic-peptides gave good protection when preincubated with granule extract for brief periods before intrapulmonary instillation. Lesser, but still significant, protection was observed in the absence of preincubation. Protection was not simply due to addition of exogenous proteins to the granule extract because substitution of goat immunoglobulin for pneumococcal fraction was ineffective. These results suggest that pneumococcal elastase-inhibitors, recently described by us, may play a role in minimizing lung injury during pneumococcal pneumonia.
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PMID:A new elastase inhibitor from Streptococcus pneumoniae protects against acute lung injury induced by neutrophil granules. 384 26

We monitored the plasma elastase alpha 1-proteinase inhibitor complex levels in 21 patients with primary lung cancer who received combination chemotherapy with or without recombinant human granulocyte colony-stimulating factor (rhG-CSF), and 15 normal nonsmokers as controls. Of the 21 patients, 14 received combination chemotherapy without rhG-CSF (among them, 6 developed pneumonia) and 7 received combination chemotherapy with rhG-CSF (among them, 1 developed pneumonia). We measured peripheral WBC counts, C-reactive protein (CRP) levels, plasma elastase alpha 1-proteinase inhibitor complex (complex) levels, and complex/WBC values during cancer chemotherapy. In patients who received cancer chemotherapy without rhG-CSF and had no complications (n = 8), WBC values decreased after chemotherapy, and then gradually increased. Complex levels also decreased slightly after chemotherapy and gradually recovered. The value obtained from dividing the complex concentration by WBC count (complex/WBC value) remained stable during cancer chemotherapy. In patients who received cancer chemotherapy with rhG-CSF and had no complications (n = 6), WBC values decreased after chemotherapy, and then rapidly increased to abnormally high values. Complex levels also decreased slightly after chemotherapy and rapidly increased to abnormally high values together with the WBC counts. The complex/WBC values remained stable during cancer chemotherapy. In patients who developed pneumonia during cancer chemotherapy with or without rhG-CSF (n = 7), their complex levels, complex/WBC values, and CRP levels were elevated at the onset of pneumonia. The maximum complex levels (the highest levels during chemotherapy) were significantly higher in patients who received cancer chemotherapy with rhG-CSF and did not develop pneumonia (583.1 +/- 114.5 ng/mL) and in patients who developed pneumonia during cancer chemotherapy (516.7 +/- 113.2 ng/mL), compared with normal nonsmokers (130.2 +/- 5.5, p < 0.01) and patients who received cancer chemotherapy without rhG-CSF and did not develop complications (211.5 +/- 23.3, p < 0.01). The maximum complex/WBC values were not increased in patients who received cancer chemotherapy with rhG-CSF (0.08 +/- 0.01) and patients who received cancer chemotherapy without rhG-CSF (0.092 +/- 0.01, p < 0.01). The maximum complex/WBC values were significantly higher in patients with pneumonia (0.56 +/- 0.12) compared with normal nonsmokers (0.026 +/- 0.002, p < 0.01) and patients without complications. These findings suggest that although rhG-CSF increases total plasma elastase burden, increased release of neutrophil elastase from individual neutrophils does not take place in vivo in the absence of pneumonia.
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PMID:Measurements of plasma elastase alpha 1-proteinase inhibitor complexes in patients receiving cancer chemotherapy with granulocyte colony-stimulating factor. 753 56

Low-dose methylprednisolone and antibiotics were used to treat 30 patients with aspiration pneumonia, in a prospective, randomized, double-blind trial with placebo control. All patients received clindamycin phosphate 1200 mg per day. In addition, 15 patients received methylprednisolone 20 mg per day for three days and the other 15 patients received placebo according to the same schedule. In the methyl prednisolone group, CRP had decreased (p < 0.05) from 12.7 +/- 9.8 to 6.4 +/- 5.4 mg/dl day 4, neutrophil elastase had decreased (p < 0.05) from 402 +/- 304 to 231 +/- 64 micrograms/dl by day 4 and to 184 +/- 59 micrograms/dl by day 7, maximum body temperature had decreased (p < 0.01) from 37.9 +/- 1.1 to 36.8 +/- 0.6 degrees C by day 7, and the pneumonia score had improved (p < 0.01) from 11.8 +/- 3.0 to 8.6 +/- 2.4 by day 4. In the placebo group, there were no significant improvements by those days. We conclude that low-dose methylprednisolone therapy with antibiotics is effective against aspiration pneumonia.
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PMID:[Treatment of aspiration pneumonia with low-dose methylprednisolone and antibiotics]. 769 68

Bacterial infections of the respiratory tract are a major cause of morbidity and mortality in elderly people. The inflammatory response to such infection is an important protective process and has been suggested to be less effective in elderly patients. To investigate the inflammatory response in respiratory infections acquired in the community by elderly people we studied 52 consecutive patients who met the criteria for either a non-pneumonic chest infection or pneumonia. After exclusion, 41 patients were available for evaluation, with 25 fulfilling the criteria of pneumonia and 16 the criteria of chest infection. Pyrexia was a feature of the patients with pneumonia. Circulating levels of neutrophil elastase-alpha-1-antitrypsin complex and C-reactive protein were greater in the patients with pneumonia than in those with a chest infection and were reduced following antibiotic treatment. No changes occurred in the chest infection group for these markers of inflammation. In both groups, a further neutrophil granule protein, lactoferrin, was unaffected by antibiotic treatment. This study indicates that elderly patients with pneumonia can initiate an appropriate inflammatory response as demonstrated by clinical indicators and circulating mediators of the inflammatory response.
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PMID:Inflammatory markers of lower respiratory tract infection in elderly people. 797 76

In a case-control study in 398 neonates the value of measuring the levels of neutrophil elastase-alpha 1 proteinase inhibitor (EPI) for early diagnosis of neonatal infection was studied in comparison to the commonly used parameters of leukocyte count, ratio of immature to total granulocytes and C-reactive protein levels. Investigations were performed on day 1 or day 6 of life. On the basis of the clinical findings patients were allocated to one of the three following groups: healthy neonates (group A), neonates with local infections such as pneumonia or skin infection (group B) or neonates with septicemia as demonstrated by a positive blood culture (group C). The median EPI levels (with range) measured on day 1 were: group A 40 (15-65) micrograms/l, group B 120 (80-260) micrograms/l, group C225 (140-355) micrograms/l. The levels on day 6 were: group A 27.5 (5-55) micrograms/l, group B 105 (65-370) micrograms/l, group C 182.5 (74-450) micrograms/l. EPI thus discriminated well between healthy neonates and neonates with infection, but not between neonates with infection and neonates with septicemia.
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PMID:Value of measurement of neutrophil elastase-alpha 1 proteinase inhibitor levels in the early diagnosis of neonatal infection. 840 19

Because interleukin 8 (IL-8) is a potent neutrophil chemotactic and activating cytokine, we investigated IL-8 production in relation to neutrophil migration and elastase release in the human lung during unilateral community-acquired pneumonia (CAP). In 17 patients, the local response in the involved lung was compared with that in the contralateral, noninvolved lung, and with the systemic response. Eight healthy volunteers served as controls. IL-8, total neutrophil elastase (NE), free elastase activity, alpha 1-antitrypsin (alpha 1-AT), and total leukocyte and neutrophil counts were evaluated in bronchoalveolar lavage fluids (BALF). Mean IL-8 concentrations in BALF from the involved lungs of the patients were significantly greater than those in BALF from the noninvolved lung or from controls (p < or = 0.001). By contrast, the serum IL-8 concentration was not different in patients and in controls. Total NE and alpha 1-AT concentrations were increased in BALF from the involved lung as compared with the noninvolved lung or controls (p < or = 0.001). The elastase-inhibitory capacity of alpha 1-AT in BALF was impaired in the involved lung of seven of the 14 patients as compared with the controls, leading to free elastase activity in the involved lung of all patients with CAP. Plasma total NE concentrations were significantly greater in the CAP patients than in the controls. IL-8 concentrations in BALF correlated positively with total leukocyte counts, absolute numbers and percentages of neutrophils, total NE concentrations, and free elastase activity. Our results suggest that during unilateral CAP, locally produced IL-8 may trigger neutrophil accumulation and activation, thus contributing to a local elastase/antielastase imbalance within the site of infection.
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PMID:Compartmentalized IL-8 and elastase release within the human lung in unilateral pneumonia. 854 40


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