Lung lavage fluid from patients with α1-proteinase inhibitor deficiency or chronic obstructive bronchitis: anti-elastase function and cell profile

1987 ◽  
Vol 72 (3) ◽  
pp. 373-381 ◽  
Author(s):  
Heather M. Morrison ◽  
Johannes A. Kramps ◽  
David Burnett ◽  
R. A. Stockley
Keyword(s):  
Bronchoalveolar Lavage ◽  
Neutrophil Elastase ◽  
Proteinase Inhibitor ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Chronic Obstructive ◽  
Pancreatic Elastase ◽  
Functional Assays ◽  
Porcine Pancreatic Elastase ◽  
Cell Profile

1. The anti-elastase composition of bronchoalveolar lavage (BAL) fluid from (α1-proteinase inhibitor (α1PI) deficient and bronchitic patients was determined by immunological and functional assays, together with the cell profile of the BAL fluid. 2. α1PI, anti-leucoprotease and α2-macroglobuin were present in all the samples. BAL fluid α1PI concentrations were significantly lower in the group with serum α1PI deficiency. 3. Lavage fluid from α1PI deficient subjects inhibited less porcine pancreatic elastase than bronchitic BAL fluid (P < 0.005). However, the α1PI was only about 50% active as an inhibitor in both groups. 4. There was no difference in the amount of neutrophil elastase (NE) inhibited per ml of lavage fluid or per mol of the measured inhibitors in the secretions, but both groups inhibited more enzyme than would be expected for these inhibitors (α1PI deficient: median 4.78 mol of NE/mol of known inhibitors, range 0.88–78.80; bronchitic: 1.14, 0.21–4.66), suggesting that an additional inhibitor is present. 5. The total leucocyte and neutrophil counts were elevated (2P < 0.01) in the lavages of α1PI deficient patients, suggesting a greater potential elastase burden than subjects with normal α1PI.

Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin-mediated mechanism

2000 ◽  
Vol 89 (4) ◽  
pp. 1397-1402 ◽  
Author(s):  
M. Scuri ◽  
R. Forteza ◽  
I. Lauredo ◽  
J. R. Sabater ◽  
Y. Botvinnikova ◽  
...  
Keyword(s):  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Inflammatory Diseases ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Human Neutrophil Elastase ◽  
Elastase Inhibitor ◽  
Pancreatic Elastase ◽  
Asthmatic Patients ◽  
Porcine Pancreatic Elastase

Neutrophil elastase has been linked to inflammatory lung diseases such as chronic obstructive pulmonary disease, adult respiratory distress syndrome, emphysema, and cystic fibrosis. In guinea pigs, aerosol challenge with human neutrophil elastase causes bronchoconstriction, but the mechanism by which this occurs is not completely understood. Our laboratory previously showed that human neutrophil elastase releases tissue kallikrein (TK) from cultured tracheal gland cells. TK has been identified as the major kininogenase of the airway and cleaves both high- and low-molecular weight kininogen to yield lysyl-bradykinin. Because inhaled bradykinin causes bronchoconstriction and airway hyperresponsiveness in asthmatic patients and allergic sheep, we hypothesized that elastase-induced bronchoconstriction could be mediated by bradykinin. To test this hypothesis, we measured lung resistance (Rl) in sheep before and after inhalation of porcine pancreatic elastase (PPE) alone and after pretreatment with a bradykinin B2 antagonist (NPC-567), the specific human elastase inhibitor ICI 200,355, the histamine H1-antagonist diphenhydramine hydrochloride, the cysteinyl leukotriene 1 receptor antagonist montelukast, or the cyclooxygenase inhibitor indomethacin. Inhaled PPE (125–1,000 μg) caused a dose-dependent increase in Rl. Aerosol challenge with a single 500 μg dose of PPE increased Rlby 132 ± 8% over baseline. This response was blocked by pretreatment with NPC-567 and ICI-200,355 ( n = 6; P < 0.001), whereas treatment with dyphenhydramine hydrochloride, montelukast, or indomethacin failed to block the PPE-induced bronchoconstriction. Consistent with pharmacological data, TK activity in bronchial lavage fluid increased 134 ± 57% over baseline ( n = 5; P < 0.02). We conclude that, in sheep, PPE-induced bronchoconstriction is in part mediated by the generation of bradykinin. Our findings suggest that elastase-kinin interactions may contribute to changes in bronchial tone during inflammatory diseases of the airways.

Cigarette smoking, emphysema, and damage to alpha 1-proteinase inhibitor

1994 ◽  
Vol 266 (6) ◽  
pp. L593-L611 ◽  
Author(s):  
M. D. Evans ◽  
W. A. Pryor
Keyword(s):  
Cigarette Smoke ◽  
Proteinase Inhibitor ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Tissue Destruction ◽  
Phagocytic Cells ◽  
Lung Fluid

The proteinase-antiproteinase theory for the pathogenesis of emphysema proposes that the connective tissue destruction associated with emphysema arises from excessive proteinase activity in the lower respiratory tract. For this reason, the relative activities of neutrophil elastase and alpha 1-proteinase inhibitor (alpha 1-PI) are considered important. Most emphysema is observed in smokers; therefore, alpha 1-PI has been studied as a target for smoke-induced damage. Damage to alpha 1-PI in lung fluid could occur by several mechanisms involving species delivered to the lung by cigarette smoke and/or stimulated inflammatory cells. Oxidative damage to alpha 1-PI has received particular attention, since both cigarette smoke and inflammatory cells are rich sources of oxidants. In this article we review almost two decades of research on mechanistic studies of damage to alpha 1-PI by cigarette smoke and phagocytic cells in vitro, studies emphasizing the importance of elastinolytic activity in the pathogenesis of emphysema in vivo and studies of human lung lavage fluid to detect defects in alpha 1-PI at the molecular and functional levels.

The form and Function of Alpha1 Proteinase Inhibitor in Normal Lung Lavage Fluid

1987 ◽  
Vol 73 (s17) ◽  
pp. 21P-21P
Author(s):  
S C Afford ◽  
D Burnett ◽  
P Davis Cory ◽  
E J Campbell ◽  
R A Stockley
Keyword(s):  
Proteinase Inhibitor ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Normal Lung ◽  
Form And Function ◽  
And Function

Rapid screening for deficiency of alpha 1-proteinase inhibitor.

1989 ◽  
Vol 35 (9) ◽  
pp. 1971-1975 ◽  
Author(s):  
C Lloyd ◽  
J Travis
Keyword(s):  
Human Plasma ◽  
Inhibitory Activity ◽  
Proteinase Inhibitor ◽  
Rapid Screening ◽  
Early Screening ◽  
Pancreatic Elastase ◽  
Low Concentrations ◽  
Normal Individuals ◽  
Porcine Pancreatic Elastase ◽  
Alpha 1 Antitrypsin

Abstract This rapid screening procedure for detection of low but functional elastase-inhibitory activity in human plasma is based on the fact that incubation of excess porcine pancreatic elastase (EC 3.4.21.36) with plasma results in formation of a complex with active alpha 1-proteinase inhibitor (alpha 1PI, also called alpha 1-antitrypsin). In normal individuals all of the elastase is complexed, leaving no free enzyme to hydrolyze the elastase substrate, and the reaction mixture remains clear. Because individuals homozygous for the Z allele have relatively low concentrations of alpha 1PI, their plasma cannot complex all of the elastase in the assay. The uncomplexed enzyme hydrolyzes the elastase-specific p-nitroanilide substrate, producing a yellow reaction mixture. Use of this simple assay for early screening of individuals for alpha 1PI deficiency may substantially decrease the number of untreated cases of familial emphysema, a disorder that develops as a result of a genetically derived proteinase-proteinase inhibitor imbalance.

scholarly journals Bronchoalveolar Lavage Fluid from COPD Patients Reveals More Compounds Associated with Disease than Matched Plasma

Metabolites ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 157 ◽  
Author(s):  
Eitan Halper-Stromberg ◽  
Lucas Gillenwater ◽  
Charmion Cruickshank-Quinn ◽  
Wanda Kay O’Neal ◽  
Nichole Reisdorph ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Cell Metabolism ◽  
Lavage Fluid ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Exacerbations ◽  
False Discovery ◽  
Copd Patients ◽  
Clinical Covariates

Smoking causes chronic obstructive pulmonary disease (COPD). Though recent studies identified a COPD metabolomic signature in blood, no large studies examine the metabolome in bronchoalveolar lavage (BAL) fluid, a more direct representation of lung cell metabolism. We performed untargeted liquid chromatography–mass spectrometry (LC–MS) on BAL and matched plasma from 115 subjects from the SPIROMICS cohort. Regression was performed with COPD phenotypes as the outcome and metabolites as the predictor, adjusted for clinical covariates and false discovery rate. Weighted gene co-expression network analysis (WGCNA) grouped metabolites into modules which were then associated with phenotypes. K-means clustering grouped similar subjects. We detected 7939 and 10,561 compounds in BAL and paired plasma samples, respectively. FEV1/FVC (Forced Expiratory Volume in One Second/Forced Vital Capacity) ratio, emphysema, FEV1 % predicted, and COPD exacerbations associated with 1230, 792, eight, and one BAL compounds, respectively. Only two plasma compounds associated with a COPD phenotype (emphysema). Three BAL co-expression modules associated with FEV1/FVC and emphysema. K-means BAL metabolomic signature clustering identified two groups, one with more airway obstruction (34% of subjects, median FEV1/FVC 0.67), one with less (66% of subjects, median FEV1/FVC 0.77; p < 2 × 10−4). Associations between metabolites and COPD phenotypes are more robustly represented in BAL compared to plasma.

Assessment of cellular profile and lung function with repeated bronchoalveolar lavage in individual mice

2000 ◽  
Vol 2 (1) ◽  
pp. 29-36 ◽  
Author(s):  
DIANNE M. WALTERS ◽  
MARSHA WILLS-KARP ◽  
WAYNE MITZNER
Keyword(s):  
Lung Function ◽  
Bronchoalveolar Lavage ◽  
Inflammatory Cells ◽  
Lung Lavage ◽  
Whole Lung Lavage ◽  
Genomic Studies ◽  
Respiratory System Resistance ◽  
Baseline Values ◽  
Different Strains ◽  
Cell Profile

Walters, Dianne M., Marsha Wills-Karp, and Wayne Mitzner. Assessment of cellular profile and lung function with repeated bronchoalveolar lavage in individual mice. Physiol. Genomics 2: 29–36, 2000.—In this study, we sought to develop procedures that would enable repeated bronchoalveolar lavage (BAL) in individual mice on multiple occasions. To achieve this objective, we first developed the procedures that would allow individual mice to survive a whole lung lavage, and then tested whether, on subsequent days, there was an effect of this initial BAL on the cell profile, lung permeability, and baseline respiratory function. Our results demonstrate that the repeated lavage procedure can be readily carried out in individual mice of different strains on multiple occasions. The lavage procedure itself results in immediate increases in respiratory system resistance and concomitant decreases in compliance, but these parameters return to prelavage values by the 2nd or 3rd day postlavage. Lavage also induces variable increases in inflammatory cells depending on the strain used. However, in all three strains examined here (A/J, BALB/c, and C3H/HeJ), inflammatory cell numbers returned to baseline values within 3 days after an initial lavage procedure. The ability to perform repeated BAL in individual mice should prove to be an extremely useful tool in a variety of functional genomic studies in the lung.

scholarly journals The effect of induced sputum and bronchoalveolar lavage fluid from patients with chronic obstructive pulmonary disease on neutrophil migration in vitro

Medicina ◽  
2010 ◽  
Vol 46 (5) ◽  
pp. 315 ◽  
Author(s):  
Agnė Babušytė ◽  
Jolanta Jeroch ◽  
Rimantas Stakauskas ◽  
Kristina Stravinskaitė ◽  
Kęstutis Malakauskas ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Neutrophil Migration ◽  
Lavage Fluid ◽  
Interleukin 8 ◽  
Induced Sputum ◽  
Chronic Obstructive ◽  
Healthy Individuals ◽  
Copd Patients

Objective. The aim of study was to investigate a chemotactic effect of induced sputum and bronchoalveolar lavage fluid on blood neutrophils in patients with chronic obstructive pulmonary disease (COPD) and healthy individuals. Material and methods. Forty-three smokers with COPD, 19 ex-smokers with COPD, 13 healthy smokers, and 17 healthy nonsmokers were recruited to the study. Neutrophils were isolated from peripheral blood of study individuals. For the same experimental conditions, pooled induced sputum and bronchoalveolar lavage fluid of 20 COPD patients were used. Neutrophil chemotaxis in vitro was performed in cell-transmigration chamber. Substances tested for chemoattraction (interleukin-8, induced sputum, bronchoalveolar lavage fluid directly or in addition to interleukin-8) were added to lower wells. Upper wells were filled with 2.5×106/mL of neutrophil culture and incubated for 2 hours. Migration was analyzed by flow cytometry. Results. Interleukin-8 (10–100 ng/mL) induced a dose-dependant neutrophil migration in all the groups. Only 100 ng/L of interleukin-8 induced more intensive chemotaxis of neutrophils from COPD smokers as compared to ex-smokers (P<0.05). Such difference between healthy individuals was obtained using 30 ng/mL of interleukin-8 (P<0.05). Induced sputum/interleukin-8 (10–100 ng/mL), as well as induced sputum directly, induced neutrophil migration (P<0.05). Chemotaxis of neutrophils isolated from COPD patients and healthy nonsmokers did not depend on additional interleukin-8 concentration. Bronchoalveolar lavage fluid/interleukin-8 (30–100 ng/mL) induced more intensive migration of neutrophils from COPD patients than bronchoalveolar lavage fluid (P<0.05) alone. Conclusions. Migration of neutrophils isolated from patients with COPD was more intensive compared to healthy individuals. Induced sputum and bronchoalveolar lavage fluid directly and with addition of interleukin-8 stimulated chemotaxis, and it was higher in neutrophils from COPD patients. Migration of neutrophils did not depend on smoking status.

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