Elastase In Patients Research Articles

Neutrophil elastase, von willebrand factor, soluble thrombomodulin and percutaneous oxygen in peripheral atherosclerosis

To test the hypothesis that endothelial cell damage and hypoxia are related to the activity of neutrophil elastase in patients with peripheral atherosclerosis. A cross-sectional serological study in a tertiary referral, University Hospital. Venous blood was obtained from 22 patients with peripheral vascular disease and an equal number of age and sex matched controls. Neutrophil elastase and two markers of endothelial cell damage (von Willebrand factor and soluble thrombomodulin) were measured in plasma by ELISA. Hypoxia was measured by percutaneous oxygen (by oximeter) at the dorsum of the foot. Patients had higher von Willebrand factor, higher soluble thrombomodulin and higher elastase but lower percutaneous oxygen (all p < 0.001). In the patient's group, there were significant inverse correlates between von Willebrand factor and percutaneous oxygen (p = 0.004) and between soluble thrombomodulin and percutaneous oxygen (p = 0.011) while elastase correlated positively with soluble thrombomodulin (p = 0.023). Our data support the hypothesis that release of elastase from activated neutrophils relates to endothelial cell damage. This may contribute to hypoxia and may result in the deterioration in clinically assessed atherosclerosis.

Activity of leukocyte elastase in patients' plasma is a significant indicator of atopic diseases

It is commonly known that activation of plasma kallikrein-kinin system is of great importance in the pathogenesis of atopic diseases. Plasma kallikrein most likely activates other arginine-esterases in human plasma. Diagnostic and prognostic values of the total arginine-esterase activity and the activity of leukocyte elastase (LE) in plasma of patients with allergic rhinitis (AR), atopic bronchial asthma (ABA) and atopic dermatitis (AD) were examined in this study. Our results demonstrate that the level of arginine-esterase activity was slightly elevated only in plasma of patients with ABA (424 ± 24; N-360 ± 20 mU/ml), but not with AR and AD. Elastase-like activity in human plasma proved to be a far more informative indicator of the atopic states than arginine-esterase activity. In plasma of patients with AR, ABA and AD the activity of LE exceeded the normal level in 1.7, 1.8, and 2.4 times, respectively. Treatment of these atopic states with Ditec (Boehringer Ingelheim) led to some improvements of the patient' states. The main component of this drug (disodium chromoglycate) inhibited the activity of leukocyte elastase in experiments in vitro.

Soluble thrombomodulin increases in patients with disseminated intravascular coagulation and in those with multiple organ dysfunction syndrome after trauma: role of neutrophil elastase.

Our goal was to investigate the role of soluble thrombomodulin (TM) and neutrophil elastase in patients with trauma. This study is a prospective case-control study. Forty-seven trauma victims, 14 with disseminated intravascular coagulation (DIC), 5 with multiple organ dysfunction syndrome (MODS), and 28 control patients without DIC or MODS were the participants. Soluble TM and neutrophil elastase (elastase-alpha1-proteinase inhibitor complex) were measured on the day of the injury, and on the first, third, and fifth days after admission. The results of these measurements and demographic data were compared among the groups, and correlations between the soluble TM and the neutrophil elastase were examined. The DIC patients were classified into subgroups of survivors (n = 5) and nonsurvivors (n = 9), and the changes of the soluble TM between the subgroups were then studied. A high incidence of DIC patients encountered MODS complications (12 of 14, 86%). The DIC patients had higher Injury Severity Scores (ISSs) than the other patients. The levels of soluble TM and neutrophil elastase significantly increased on the day of admission in the patients with DIC and also in those with MODS (p < 0.05 vs. control patients) and continued to show markedly high values until the fifth day of admission in the patients with DIC. In the DIC patients, the levels of soluble TM were higher in the nonsurvivors than in the survivors (p < 0.05 on the third and the fifth days of admission). In all patients, there was weak but statistically significant correlation between peak levels of soluble TM and ISS (r2 = 0.125, p < 0.025). Comparison of the levels of soluble TM and neutrophil elastase in the patients with DIC or MODS demonstrated an excellent correlation (r2 = 0.718 and r2 = 0.714, respectively). Soluble TM as a novel endothelial cell injury marker increases in patients with DIC and also in those with MODS after trauma. Neutrophil elastase may be involved in the pathogenesis of the injury. Soluble TM is a marker of the severity of injury and is a good predictor of MODS.

Role of the Neutrophil in Abdominal Aortic Aneurysm Development

Elastase release by neutrophils has been implicated in the etiology of abdominal aortic aneurysm (AAA). The present study investigated whether neutrophils in patients with AAA actively synthesize the neutrophil elastase enzyme and the effect of elastin-derived peptides on neutrophil elastase release. Total neutrophil elastase in patients with AAA was significantly higher than in those with aortic occlusive disease and controls. The neutrophil elastase gene was not expressed in any patient group. Elastin-derived peptides induced elastase release, which was significantly higher in patients with AAA than in those with aortic occlusive disease and controls. These data indicate that the peptides of elastin degradation stimulate the release of elastase, but that continuing production of elastase is absent in circulating neutrophils. It is concluded that: (1) neutrophils do not actively synthesize elastase but act as 'mules' or carriers of the enzyme; and (2) elastin breakdown products stimulate the release of elastase at the aortic wall by circulating neutrophils, which in patients with AAA have a predetermined increased amount of elastase.

Plasma polymorphonuclear elastase in patients with hyperthyroidism.

We studied plasma polymorphonuclear elastase (PMNE) levels before and during methimazole treatment in patients with hyperthyroidism. Plasma PMNE levels in patients with hyperthyroidism were significantly higher than those of normal subjects and patients with thyroid adenoma. Plasma PMNE levels in patients with Graves' disease were significantly reduced when their thyroid functions after methimazole treatment were normal, compared with the levels of the patients before treatment. In patients with hyperthyroidism there was a significant positive correlation between plasma PMNE and serum FT3, but no correlation between plasma PMNE and serum TRAb. The results suggested that PMNE was secreted from blood neutrophil in hyperthyroid state patients with Graves' disease and that it was beneficial for helping determining peripheral thyroid function.

Zum Verhalten der Leukozytenelastase bei chronisch entzündlichen Gaumenmandelerkrankungen*

Inflammatory diseases may lead to local tissue injury due to an imbalance between leukocyte elastase and protease inhibitors (alpha-1-antitrypsin, alpha-2-macroglobulin). Hence, we determined the plasma level of elastase in patients with chronic tonsillitis using an enzyme-linked immunoassay and compared the results with those obtained from controls. There was a significant elevation of leukocyte elastase in patients with chronic inflammation of the tonsils compared with our controls. The sensitivity and specificity of the elastase assay characterise this method as a reliable one. Hence, the determination of leukocyte elastase in peripheral blood can be useful if the indication for tonsillectomy is in question.

Circulating inhibitor bound elastase in patients with ankylosing spondylitis and rheumatoid arthritis and the influence of sulphasalazine treatment.

The plasma concentration of granulocyte elastase in complex with alpha 1 proteinase inhibitor was determined in 42 patients with ankylosing spondylitis (AS) and 33 patients with rheumatoid arthritis (RA). Significantly raised levels of plasma elastase were found in patients with RA, whereas patients with AS had normal values. No correlation was seen between the elastase values and erythrocyte sedimentation rate (ESR), serum haptoglobin, immunoglobulins, or polymorphonuclear cell (PMN) count in either of the patient groups. A correlation was found between the Ritchie index and plasma elastase in patients with RA. After three months' treatment with sulphasalazine a clinical improvement was seen and this paralleled a reduction of the acute phase reaction in both patient groups. A reduction of the circulating elastase values was seen in the patients with RA, whereas no change was seen in patients with AS.

Circulating human leucocyte elastase in patients with inflammatory bowel disease.

The plasma concentration of human leucocyte elastase (HLE), measured by enzyme immunoassay as the complex with alpha 1-proteinase inhibitor, was determined in 94 patients with active and inactive inflammatory bowel disease. In Crohn's disease and in ulcerative colitis human leucocyte elastase levels were raised significantly above normal when the disease was active, and fell on remission. The mean human leucocyte elastase level in 31 cases of active Crohn's disease was significantly greater than the mean human leucocyte elastase level in 23 patients with active ulcerative colitis (p = 0.013). The values of human leucocyte elastase correlated significantly with Crohn's disease activity index scores (p = 0.05) and with the circulating concentration of C-reactive protein (p less than 0.05 and p less than 0.01 for ulcerative colitis and Crohn's disease respectively), but not with the erythrocyte sedimentation rate. These results indicate that the concentration of human leucocyte elastase in the plasma of patients with inflammatory bowel disease reflects the activity of their intestinal disease and suggest that serial measurements of human leucocyte elastase may be useful in the assessment and clinical management of these conditions.

Fibrinogen split products, antiproteases and granulocytic elastase in patients with lung cancer

Fibrinogen degradation products (FDP) were found in the sera of 40% of patients with lung cancer before therapy. In patients with metastatic disease, 22 out of 26 had FDP in the serum. There was no sign of general intravascular coagulation and fibrinolysis. Plasminogen, antithrombin III and fibrinogen levels were normal or higher. The antiproteases α 1-antichymotrypsin, inter-α-trypsin inhibitor, and α 2-macroglobulin, were normal, but α 1-antitrypsin was found to be increased especially in patients with metastatic disease. In these patients a granulocytic elastase (ELP) could be demonstrated to be bound to α 1-antitrypsin. This ELP which may be released from granulocytes by circulating immune complexes, is able to digest fibrin and/or fibrinogen, leading to the formation of split products similar to those induced by plasmin. Furthermore, it is shown that the determination of FDP, ELP and α 1-antitrypsin ( α 1 - AT) may have a prognostic value in lung cancer patients.

Interrelationships between neutrophil elastase, serum alpha, -antitrypsin, lung function and chest radiography in patients with chronic airflow obstruction.

We assayed protease and elastase activity of lysosomal granules of purified neutrophil suspensions in 58 patients with chronic irreversible airflow obstruction and compared them to 26 healthy control subjects. Denatured hemoglobin and tritiated elastin were used as substrates for protease and elastase assays. Forty-two patients had M antitrypsin phemotype, five had MS, and 11 had Z variant (five were homozygotes and six were heterozygotes). We did not find significant differences in mean lysosomal elastase or protease activity between patients with normal antitrypsin and control subjects; however, a few patients had concentrations of neutrophil elastase that exceeded the range among control subjects. There was no significant correlation between neutrophil protease or elastase activity and age, smoking, degree of airway obstruction, diffusing capacity, lung elastic recoil, or radiologic presence of emphysema in patients with M and MS antitrypsin. In patients with Z variant antitrypsin, protease and elastase concentrations per unit of lysosomal protein were not significantly different from those in control subjects or M patients; however, both elastase and protease content per 108 neurtophils was significantly higher in homozygous and heterozygous Z patients as compared to normalsubjects and M patients, which suggest an increase in the neutrophil content of protease and elastase in patients with Z antitrypsin deficiency. These results suggest that hte concentrations of protease and elastase in neutrophils do not appear to interact as additive risk factors in the pulmonary impairment of most patients with chronic airflow obstruction, but may be of importance as risk factors in patients with Z or MZ phenotype and in a few patients with M phenotype.