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Enhanced generation of leukotriene B4 by neutrophils stimulated by unopsonized zymosan and by calcium ionophore after exercise-induced asthma. 1988

J P Arm, and C E Horton, and F House, and T J Clark, and B W Spur, and T H Lee
Department of Medicine, United Medical School, Guy's Hospital, London, United Kingdom.

The generation of LTB4 by peripheral blood neutrophils (PMN) isolated before and for as long as 6 h after exercise-induced asthma (EIA) has been analyzed. Three and 6 h after the development of EIA, PMN isolated from 10 asthmatic subjects and stimulated in vitro by 2 x 10(8) and 4 x 10(8) zymosan particles per 2 x 10(6) PMN demonstrated a 12- and 4-fold enhancement, respectively, in the production of immunoreactive LTB4 as compared with PMN isolated before exercise. At 6 h after EIA, there was a redistribution of generated LTB4 such that 30 to 40% of LTB4 produced by zymosan-activated PMN was released extracellularly as compared with 10% before exercise. There was no significant enhancement in the generation of LTB4 by unstimulated PMN at any time point after exercise. Resolution by reverse-phase high performance liquid chromatography (HPLC) of products from [3H]arachidonic-acid-labeled and zymosan-activated PMN demonstrated that, in addition to LTB4, there was enhanced metabolism to 6-trans-LTB4, omega-oxidation metabolites of LTB4 and 5-HETE. Stimulation of PMN with 10 microM A23187 revealed a 2-, 6-, and 5-fold enhancement in the production of LTB4, 6-trans-LTB4, and 5-HETE, respectively, at 6 h after EIA, as measured by integrated ultraviolet absorbance after HPLC. There was no significant enhancement in LTB4 generation by PMN in 6 asthmatic subjects after methacholine-induced bronchospasm, and after exercise in 6 subjects who did not develop asthma. The augmentation of PMN LTB4 generation in EIA correlated with the extent of the early decrease in SGaw.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007975 Leukotriene B4 The major metabolite in neutrophil polymorphonuclear leukocytes. It stimulates polymorphonuclear cell function (degranulation, formation of oxygen-centered free radicals, arachidonic acid release, and metabolism). (From Dictionary of Prostaglandins and Related Compounds, 1990) 5,12-HETE,5,12-diHETE,LTB4,Leukotriene B,Leukotriene B-4,Leukotrienes B,5,12 HETE,5,12 diHETE,B-4, Leukotriene,Leukotriene B 4
D008297 Male Males
D008688 Methacholine Compounds A group of compounds that are derivatives of beta-methylacetylcholine (methacholine). Compounds, Methacholine
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D001985 Bronchial Provocation Tests Tests involving inhalation of allergens (nebulized or in dust form), nebulized pharmacologically active solutions (e.g., histamine, methacholine), or control solutions, followed by assessment of respiratory function. These tests are used in the diagnosis of asthma. Allergen Bronchial Provocation Tests,Allergen Challenge, Endobronchial,Antigen Bronchial Provocation Tests,Bronchial Allergen Challenge,Bronchial Challenge Tests,Inhalation Provocation Tests,Provocation Tests, Bronchial,Endobronchial Challenge Tests,Allergen Challenge, Bronchial,Allergen Challenges, Bronchial,Allergen Challenges, Endobronchial,Bronchial Allergen Challenges,Bronchial Challenge Test,Bronchial Provocation Test,Challenge Test, Bronchial,Challenge Test, Endobronchial,Challenge Tests, Bronchial,Challenge Tests, Endobronchial,Challenge, Bronchial Allergen,Challenge, Endobronchial Allergen,Challenges, Bronchial Allergen,Challenges, Endobronchial Allergen,Endobronchial Allergen Challenge,Endobronchial Allergen Challenges,Endobronchial Challenge Test,Inhalation Provocation Test,Provocation Test, Bronchial,Provocation Test, Inhalation,Provocation Tests, Inhalation,Test, Bronchial Challenge,Test, Bronchial Provocation,Test, Endobronchial Challenge,Test, Inhalation Provocation,Tests, Bronchial Challenge,Tests, Bronchial Provocation,Tests, Endobronchial Challenge,Tests, Inhalation Provocation
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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