title: Eicosanoid mediator expression in mononuclear and polymorphonuclear cells in normal subjects and patients with atopic asthma and cystic fibrosis.
abstract: BACKGROUND
  Eicosanoids such as leukotrienes, prostaglandins, lipoxins, and 15-hydroperoxyeicosatetraenoic acid (15-HETE) cause bronchoconstriction, increased microvascular permeability, mucus secretion, and polymorph chemotaxis. These pro-inflammatory effects are important in diseases such as asthma and cystic fibrosis where the levels of mediators are increased both in the stable and acute state. A study was conducted to examine the expression of the mRNA for the enzymes of the eicosanoid pathways (5-lipoxygenase (5-LO), 5-lipoxygenase activating protein (FLAP), cyclo-oxygenases 1 and 2 (COX-1, COX-2), and 15-lipoxygenase (15-LO)) in normal subjects and in patients with stable atopic asthma and stable cystic fibrosis.
  
  
  METHODS
  Reverse transcription polymerase chain reaction (RT-PCR) was used to examine the expression of total RNA for 5-LO, FLAP, COX-1, COX-2, and 15-LO in peripheral blood polymorphonuclear cells and mononuclear cells from the three subjects groups.
  
  
  RESULTS
  The expression of mRNA for 5-LO and FLAP was similar in normal subjects and in patients with asthma and cystic fibrosis. COX-1 was increased in both cell types in asthmatic patients. COX-2 and 15-LO were increased in polymorphs of patients with atopic asthma but not in mononuclear cells. COX-2 and 15-LO were undetectable in either cell type in patients with cystic fibrosis whereas COX-1 levels in polymorphs were similar to those in patients with asthma.
  
  
  CONCLUSIONS
  The increased leukotriene production in asthma and cystic fibrosis is not explained by an increase in transcription of 5-LO and FLAP. Transcription of 15-LO and COX-2 is increased in atopic asthma. Transcription of COX-1 is increased in both atopic asthma and cystic fibrosis.
authors.affiliation: Department of Thoracic Medicine, National Heart and Lung Institute, London, UK.
authors.forename: L M
authors.initials: LM
authors.lastname: Kuitert
authors.forename: R
authors.initials: R
authors.lastname: Newton
authors.forename: N C
authors.initials: NC
authors.lastname: Barnes
authors.forename: I M
authors.initials: IM
authors.lastname: Adcock
authors.forename: P J
authors.initials: PJ
authors.lastname: Barnes
mesh_terms: D058927:5-Lipoxygenase-Activating Proteins; D000328:Adult; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003550:Cystic Fibrosis / Q000276:immunology* / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D015777:Eicosanoids; D007527:Isoenzymes; D008565:Membrane Proteins; D001093:Arachidonate 15-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases