alpha-chymotrypsin and Asthma

Topics: Acetylcysteine; Adult; Aged; Airway Obstruction; Asthma; Bicarbonates; Bronchiectasis; Bronchitis; Chronic Disease; Chymotrypsin; Clinical Trials as Topic; Deoxyribonucleases; Expectorants; Humans; Middle Aged; Peptide Hydrolases; Pneumonia; Pulmonary Emphysema; Sodium; Streptodornase and Streptokinase; Surface-Active Agents; Trypsin

On the basis of their amino acid sequences, tryptases are just another group of serine proteinases related to trypsin that happen to be expressed and stored in mast cells rather than the pancreas. On the basis of their biochemical and biological features, however, tryptases show little family likeness to trypsin and most other trypsin-like proteases. The intriguing discrepancies have been explained by the crystal structure of the tryptase tetramer. It is now clear how tryptases, by forming tetramers, have gained the ability to prevail enzymatically active in tissues, but, at the cost of an unusual narrow substrate specificity. The tryptase tetramer thus became both a (neuro)peptidase and a long-lasting initiator that orchestrates responses by the cleavage of a few key proteins, the activation of other proteases with broader specificity, and the stimulation of cellular responses. With the support of these performers, tryptase drives a variety of processes contributing to chronic inflammation and tissue remodeling, the diversity of which is still emerging.

Topics: Animals; Aprotinin; Asthma; Bronchi; Bronchoconstriction; Cell Degranulation; Chronic Disease; Chymotrypsin; Dogs; Humans; Inflammation; Inflammation Mediators; Mast Cells; Mice; Muscle, Smooth; Pancreatic Elastase; Peptide Hydrolases; Protease Inhibitors; Proteinase Inhibitory Proteins, Secretory; Proteins; Serine Endopeptidases; Serine Proteinase Inhibitors; Sheep; Species Specificity; Substrate Specificity; Tryptases

Extracts from ragweed pollen grains contain novel trypsin and chymotrypsin-like serine peptidases which are described in this report. The molecular mass of the chymotrypsin-like enzyme was 82 kDa, had a pH optimum near 9.0, and its activity was unaffected by chelating or reducing agents. It was inhibited by diisopropyl fluorophosphate (DFP), a general serine class inhibitor, and more specifically N-p-tosyl-L-phenylalanine chloromethyl ketone (TPCK), a chymotrypsin-like proteinase inhibitor. In addition to various synthetic substrates, the neuropeptides, vasoactive intestinal peptide (VIP) and substance P, which are required for normalized lung functions, were also rapidly hydrolysed. Activity toward protein substrates was not detected with the exception of the inactivation of alpha-1-proteinase inhibitor (alpha-1-PI) which occurred through cleavage within the reactive site loop. The 'trypsin-like' enzyme has a molecular mass near 80 kDa, a blocked N-terminus, a pH optimum near 9.0, and requires Ca++ for stability and activity, but not reducing agents. It is inhibited by DFP, and more specifically the trypsin-like proteinase inhibitor, N-p-tosyl-L-lysine chloromethyl ketone (TLCK). Again, activity toward protein substrates was not detected, but various synthetic substrates and biologically active peptides were efficiently cleaved. Significantly, atrial natriuretic peptide (ANP) and angiotensin 2 (ATII), whose degradation would amplify kinin activity and influence inflammatory diseases of the respiratory tract and nasal passages, were also rapidly hydrolyzed.

Topics: Allergens; Amino Acid Sequence; Asthma; Chymotrypsin; Humans; Hypersensitivity; Molecular Sequence Data; Molecular Weight; Peptides; Pollen; Serine Endopeptidases; Serine Proteinase Inhibitors; Substrate Specificity; Trypsin

Eosinophils contain many cytotoxic mediators including eosinophil peroxidase (EPO) in their granules and these mediators are released by various pathophysiological stimuli, resulting in severe damage to various epithelia. However, little is known about the intracellular mechanism of the degranulation. Here we report that eosinophils isolated from patients with bronchial asthma who were not taking corticosteroid hormone had significant amidolytic activities on Suc-Ala-Ala-Pro-Phe-MCA, and also that the activity was completely inhibited by chymostatin (1 x 10(-4) M), eglin C (1 x 10(-4) M), and peptide boronic acid (1 x 10(-4) M), indicating that eosinophils contain a chymotrypsin-like serine protease in the fraction eluted in 50 mM potassium phosphate buffer, pH 8.0 containing 2 M NaCl. Among the various types of protease inhibitors examined, one of the chymotrypsin-type proteases chymostatin (1 x 10(-4) M), but none of the other types of proteases such as leupeptin and E-64, markedly inhibited the EPO release (c.a. 60%) from eosinophils stimulated by immunoglobulin-G (2.5 mg protein/ml beads) in the presence of rhIL-5 (10 ng/ml) or platelet-activating factor (1 x 10(-7) M), although it had no effect on the release by calcium ionophore A23187 (1 x 10(-7) M).

Topics: Adult; Asthma; Cells, Cultured; Chymotrypsin; Eosinophil Peroxidase; Eosinophils; Humans; Middle Aged; Peroxidases; Protease Inhibitors

A heat-stable neutrophil chemotactic factor (NCF) has been identified in the serum of 13 atopic asthmatic subjects after treadmill exercise. Peak activity was detected at 10 min and returned to prechallenge values by 1 h. No NCF activity was detected in the sera of three nonasthmatic atopic or four normal nonatopic individuals performing the same task. NCF produced by exercise (NCFEX) had a similar time-course of release to NCF provoked by specific antigen (NCFAG). The appearance of circulating NCFEX and NCFAG closely paralleled the fall in peak expiratory flow rate/forced expiratory volume in 1 s (PEFR/FEV1). Histamine challenge in atopic asthmatics at concentrations giving a comparable change in PEFR/FEV1 to that evoked by exercise or inhaled antigen was not associated with the appearance of circulating NCF. In seven subjects NCFEX release was inhibited by prior administration of disodium cromoglycate. NCFEX and NCFAG eluted as single peaks of activity when applied separately to columns of Sephadex G-200, and both were an estimated 750,000 daltons. NCFEX and NCFAG also eluted as single peaks of activity, at between 0.15 and 0.30 M NaCl, following anion exchange chromatography on DEAE-Sephacel (pH 7.8). The isoelectric points of NCFEX and NCFAG were virtually identical (between pH 6.0 and 6.5) as determined by chromatofocusing on Polybuffer Exchanger 94. The activities of NCFEX and NCFAG were substantially reduced, in both a time- and dose-dependent fashion, after incubation with trypsin and chymotrypsin. Partially purified NCFEX and NCFAG promoted both stimulated random migration (chemokinesis) as well as directional migration (chemotaxis). These experiments indicate that NCFEX and NCFAG might be identical substances and raise the possibility that mediators by hypersensitivity are released during exercise-induced asthma in atopic subjects.

Topics: Adolescent; Adult; Asthma; Asthma, Exercise-Induced; Bronchial Provocation Tests; Cell Movement; Chemotactic Factors; Chymotrypsin; Humans; Neutrophils; Physical Exertion; Time Factors; Trypsin

Selected parametres reflecting cellular and humoral immunity were analyzed in 98, 10 year-old children, who had been hospitalized during first 2 years of life because of bronchitis. In this group, 46 children suffered from obstructive bronchitis and 52 from other types of bronchitis. Serum immunoglobulins, complement components, and antiproteolytic factor levels, T and B lymphocytes counts, leukocyte migration inhibition, and skin tests to PHA and Polyvaccine were compared and analyzed in relation to bronchial obstruction and allergic symptoms in early childhood. The results obtained did not show any significant difference when the group with obstructive type of bronchitis was compared to the rest of children studied. Some differences (increase of the percentage of EAC-FRC and decrease of the levels of the antiproteolytic factors) were noted in relation to allergic symptoms.

Topics: alpha 1-Antitrypsin; alpha-Macroglobulins; Asthma; Bronchitis; Child; Child, Preschool; Chymotrypsin; Complement C3; Complement C4; Follow-Up Studies; Humans; Immunity, Cellular; Immunoglobulins; Infant; Risk

Topics: Adolescent; Adult; Aerosols; Aged; Asthma; Bronchiectasis; Bronchitis; Chronic Disease; Chymotrypsin; Deoxyribonucleases; Female; Humans; Injections, Intramuscular; Lung Abscess; Male; Middle Aged; Pulmonary Fibrosis; Ribonucleases; Trypsin

Topics: Agar; Allergens; Asthma; Chromatography; Chymotrypsin; Dermatitis, Atopic; Egg White; Electrophoresis; Gels; Glycoproteins; Hexosamines; Hexoses; Humans; Immune Sera; Immunochemistry; Immunoelectrophoresis; Muramidase; Neuraminic Acids; Ovalbumin; Proteins; Rhinitis, Allergic, Seasonal; Skin Tests; Starch; Trypsin; Trypsin Inhibitors

Topics: Acetylcysteine; Aniline Compounds; Asthma; Bronchitis; Chronic Disease; Chymotrypsin; Expectorants; Humans; Oxytetracycline; Sputum; Toluene

Topics: Adult; Allergens; Angioedema; Antigen-Antibody Reactions; Asthma; Autacoids; Chromatography, Gel; Chymotrypsin; Dermatitis, Atopic; Female; Histamine; Humans; Hypersensitivity; Immunization, Passive; Immunoglobulin E; Kinins; Male; Perfusion; Rhinitis, Allergic, Seasonal; Skin Tests; Sodium Chloride; Trypsin

Topics: Abscess; Adult; Aged; Asthma; Chymotrypsin; Dermatitis; Female; Humans; Male; Middle Aged; Otitis; Respiratory Tract Infections; Tetracycline; Thrombophlebitis; Trypsin

Topics: Adolescent; Alpha-Globulins; Asthma; Bronchography; Child; Chymotrypsin; Eosinophilia; Feces; Female; gamma-Globulins; Humans; Leukocytosis; Male; Pneumonia; Prognosis; Skin Tests; Sweat

Topics: Adult; Asthma; Chymotrypsin; Humans; Hypersensitivity; Male; Occupational Diseases; Powders; Respiratory Function Tests; Skin Tests; Trypsin

Topics: Anti-Bacterial Agents; Antitubercular Agents; Asthma; Bronchiectasis; Bronchitis; Chloramphenicol; Chlortetracycline; Chymotrypsin; Empyema; Humans; Hydrocortisone; Kanamycin; Oxytetracycline; Penicillins; Peptide Hydrolases; Pleurisy; Pneumonia; Pulmonary Emphysema; Respiratory System; Respiratory Tract Diseases; Tuberculosis; Tuberculosis, Pulmonary

Topics: Adrenal Cortex Hormones; Aminopyrine; Asthma; Breathing Exercises; Bronchial Diseases; Chymotrypsin; Deoxyribonuclease I; Drainage; Humans; Oxygen Inhalation Therapy; Posture; Spirometry; Streptodornase and Streptokinase; Streptokinase; Syndrome; Theophylline

Topics: Asthma; Bronchitis; Chymotrypsin; Drug Therapy; Emphysema; Heart Failure; Humans; Peptide Hydrolases; Pulmonary Emphysema; Pulmonary Fibrosis; Sputum; Trypsin; Tuberculosis; Tuberculosis, Pulmonary; Viscosity

Topics: Asthma; Bronchiectasis; Bronchitis; Chymotrypsin; Humans; Lung Abscess; Peptide Hydrolases; Pneumonia; Trypsin

Topics: Asthma; Bronchitis; Chymotrypsin; Humans; Nasopharynx; Otitis Media; Otolaryngology; Rhinitis; Rhinitis, Atrophic; Sinusitis; Tracheitis; Trypsin

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Antigens; Antigens, Bacterial; Asthma; Bronchitis; Chloramphenicol; Chronic Disease; Chymotrypsin; Demeclocycline; Drug Resistance, Microbial; Enterobacter aerogenes; Erythromycin; Humans; Isoproterenol; Penicillin Resistance; Penicillins; Sputum; Staphylococcus; Streptomycin; Sulfisoxazole; Tetracycline

Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Antibiotics, Antitubercular; Asthma; Bronchial Diseases; Bronchitis; Chymotrypsin; Common Cold; Ephedrine; Epinephrine; Humans; Iodine; Sulfur

Topics: Asthma; Bronchiectasis; Bronchitis; Child; Chymotrypsin; Common Cold; Humans; Infant; Infant, Newborn; Pediatrics; Pneumonia; Whooping Cough

Topics: Antibodies; Asthma; Beta-Globulins; Blood Group Antigens; Bronchitis; Chromatography; Chymotrypsin; Dialysis; Electrophoresis; Fucose; Glycoproteins; Hexosamines; Humans; Immunoelectrophoresis; Mucous Membrane; Mucus; Neuraminic Acids; Pentoses; Pepsin A; Renal Dialysis; Serum Globulins; Sputum; Transferrin; Trypsin; Urea