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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)

Nyckelord

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

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