Rhinovirus infection increases 5-lipoxygenase and cyclooxygenase-2 in bronchial biopsy specimens from nonatopic subjects.
Rhinovirus infections cause wheeze, cough, and bronchial hyperresponsiveness. To investigate the involvement of cysteinyl-leukotrienes and prostanoids in these symptoms, bronchial biopsy specimens from 9 normal subjects (nonatopic and with no history of chronic lung disease) were immunostained for 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathway enzymes 2 weeks before and 4 days after experimental infection with human rhinovirus serotype 16. 5-LO-positive cell counts increased 9-fold (from 0.48 to 4.4 cells/mm(2); P <.05), and 5-LO-activating protein (FLAP)-positive cell counts increased 3.6-fold (from 1.8 to 6.5 cells/mm(2); P =.09). Levels of leukotriene A(4) hydrolase and leukotriene C(4) synthase were unchanged. COX-2--positive cell counts increased from 0 to 2.6 cells/mm(2) (P =.009), with no change in COX-1 levels. Increases of 3-4-fold were seen in levels of macrophages (P =.02) and mast cells (P =.07) but not of eosinophils (P >.4), and bronchoalveolar lavage fluid cysteinyl-leukotriene levels doubled (from 11.2 to 20.4 pg/mL; P =.13). Cold symptom scores correlated with bronchial immunostaining for FLAP (rho = 0.93; P =.001). In normal subjects, rhinovirus colds induce bronchial inflammation with markedly enhanced expression of 5-LO pathway proteins and COX-2.
Seymour
Michelle L
ML
Division of Respiratory Cell and Molecular Biology, University of Southampton School of Medicine, Southampton, United Kingdom.
Gilby
Natalie
N
Bardin
Philip G
PG
Fraenkel
David J
DJ
Sanderson
Gwendolyn
G
Penrose
John F
JF
Holgate
Stephen T
ST
Johnston
Sebastian L
SL
Sampson
Anthony P
AP
D001094:Arachidonate 5-Lipoxygenase / Q000032:analysis / Q000096:biosynthesis*; D001706:Biopsy; D001980:Bronchi / Q000201:enzymology* / Q000473:pathology; D003139:Common Cold / Q000188:drug therapy / Q000201:enzymology*; D051546:Cyclooxygenase 2; D003545:Cysteine / Q000032:analysis; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis*; D015289:Leukotrienes / Q000032:analysis; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000096:biosynthesis*
D007527:Isoenzymes; D015289:Leukotrienes; D008565:Membrane Proteins; C112381:cysteinyl-leukotriene; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D003545:Cysteine