Leukotriene and prostanoid pathway enzymes in bronchial biopsies of seasonal allergic asthmatics.
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.
Seymour
M L
ML
Division of Respiratory Cell & Molecular Biology, Southampton General Hospital, Southampton, United Kingdom.
Rak
S
S
Aberg
D
D
Riise
G C
GC
Penrose
J F
JF
Kanaoka
Y
Y
Austen
K F
KF
Holgate
S T
ST
Sampson
A P
AP
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
D015289:Leukotrienes; D011453:Prostaglandins; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases