title: Leukotriene and prostanoid pathway enzymes in bronchial biopsies of seasonal allergic asthmatics.
abstract: Cysteinyl-leukotrienes and prostaglandin D2 generated by the 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathways, respectively, cause bronchoconstriction, leukocyte recruitment, and bronchial hyperresponsiveness in asthma. We characterized the cellular expression of 5-LO and COX enzymes using immunohistochemistry on bronchial biopsies from 12 allergic asthmatic patients before and during seasonal exposure to birch pollen. Bronchial responsiveness (p = 0.004) and symptoms (p < 0.005) increased and peak expiratory flow (PEF; p < or = 0.02) decreased in the pollen season. In-season biopsies had 2-fold more cells immunostaining for 5-LO (p = 0.02), 5-LO-activating protein (FLAP; p = 0.04), and leukotriene (LT)A4 hydrolase (p = 0.05), and 4-fold more for the terminal enzyme for cysteinyl-leukotriene synthesis, LTC4 synthase (p = 0.02). Immunostaining for COX-1, COX-2, and PGD2 synthase was unchanged. Increased staining for LTC4 synthase was due to increased eosinophils (p = 0.035) and an increased proportion of eosinophils expressing the enzyme (p = 0.047). Macrophages also increased (p = 0.019), but mast cells and T-lymphocyte subsets were unchanged. Inverse correlations between PEF and 5-LO(+) cell counts link increased expression of 5-LO pathway enzymes in eosinophils and macrophages within the bronchial mucosa to deterioration of lung function during seasonal allergen exposure.
authors.affiliation: Division of Respiratory Cell & Molecular Biology, Southampton General Hospital, Southampton, United Kingdom.
authors.forename: M L
authors.initials: ML
authors.lastname: Seymour
authors.forename: S
authors.initials: S
authors.lastname: Rak
authors.forename: D
authors.initials: D
authors.lastname: Aberg
authors.forename: G C
authors.initials: GC
authors.lastname: Riise
authors.forename: J F
authors.initials: JF
authors.lastname: Penrose
authors.forename: Y
authors.initials: Y
authors.lastname: Kanaoka
authors.forename: K F
authors.initials: KF
authors.lastname: Austen
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
authors.forename: A P
authors.initials: AP
authors.lastname: Sampson
mesh_terms: D000328:Adult; D000397:Air Pollution / Q000009:adverse effects / Q000032:analysis; D001094:Arachidonate 5-Lipoxygenase / Q000032:analysis* / Q000276:immunology / Q000378:metabolism*; D001249:Asthma / Q000209:etiology / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D001706:Biopsy; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D004804:Eosinophils / Q000276:immunology; D005541:Forced Expiratory Volume; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D007958:Leukocyte Count; D015289:Leukotrienes / Q000032:analysis* / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D010366:Peak Expiratory Flow Rate; D011058:Pollen / Q000009:adverse effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis* / Q000276:immunology / Q000378:metabolism*; D011453:Prostaglandins / Q000032:analysis* / Q000276:immunology / Q000378:metabolism*; D012621:Seasons; D012720:Severity of Illness Index; D013548:Sweden; D013601:T-Lymphocytes / Q000276:immunology; D014197:Trees
chemical_list: D015289:Leukotrienes; D011453:Prostaglandins; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases