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.

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Dermatologi och venereologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Dermatology and Venereal Diseases hsv//eng
Adult
Air Pollution/adverse effects/analysis
Arachidonate 5-Lipoxygenase/*analysis/immunology/*metabolism
Asthma/etiology/*metabolism/*pathology/physiopathology
Biopsy
Bronchial Hyperreactivity/etiology/*metabolism/*pathology/physiopathology
Eosinophils/immunology
Forced Expiratory Volume
Humans
Hypersensitivity/etiology/*metabolism/*pathology/physiopathology
Immunohistochemistry
Leukocyte Count
Leukotrienes/*analysis/immunology/*metabolism
Macrophages/immunology
Mast Cells/immunology
Peak Expiratory Flow Rate
Pollen/*adverse effects
Prostaglandin-Endoperoxide Synthases/*analysis/immunology/*metabolism
Prostaglandins/*analysis/immunology/*metabolism
*Seasons
Severity of Illness Index
Sweden
T-Lymphocytes/immunology
Trees

Rak, Sabina,1945Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin,Institute of Internal Medicine(Swepub:gu)xraksa (författare)
Åberg, Daniel,1973Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin,Institute of Internal Medicine(Swepub:gu)xaberd (författare)
Riise, Gerdt C.,1956Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för lungmedicin och allergologi,Institute of Internal Medicine, Dept of Respiratory Medicine/Allergology(Swepub:gu)xriige (författare)
Penrose, J. F. (författare)
Kanaoka, Y. (författare)
Austen, K. F. (författare)
Holgate, S. T. (författare)
Sampson, A. P. (författare)
Göteborgs universitetInstitutionen för invärtesmedicin (creator_code:org_t)

Av författaren/redakt...: Seymour, M. L.; Rak, Sabina, 194 ...; Åberg, Daniel, 1 ...; Riise, Gerdt C., ...; Penrose, J. F.; Kanaoka, Y.; visa fler...; Austen, K. F.; Holgate, S. T.; Sampson, A. P.; visa färre...

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