EICOSANOID MEDIATOR EXPRESSION IN MONONUCLEAR AND POLYMORPHONUCLEAR CELLS IN NORMAL SUBJECTS AND PATIENTS WITH ATOPIC ASTHMA AND CYSTIC-FIBROSIS

Background - Eicosanoids such as leukotrienes, prostaglandins, lipoxin s, and 15-hydroperoxyeicosatetraenoic acid (15-HETE) cause bronchocons triction, increased microvascular permeability, mucus secretion, and p olymorph chemotaxis. These pro-inflammatory effects are important in d iseases such as asthma and cystic fibrosis where the levels of mediato rs are increased both in the stable and acute state. A study was condu cted to examine the expression of the mRNA for the enzymes of the eico sanoid pathways (5-lipoxygenase (5-LO), 5-lipoxygenase activating prot ein (FLAP), cycle-oxygenases 1 and 2 (COX-1, COX-2), and 15-lipoxygena se (15-LO)) in normal subjects and in patients with stable atopic asth ma and stable cystic fibrosis. Methods - Reverse transcription polymer ase chain reaction (RT-PCR) was used to examine the expression of tota l RNA for 5-LO, FLAP, COX-1, COX-2, and 15-LO in peripheral blood poly morphonuclear cells and mononuclear cells from the three subject group s. Results - The expression of mRNA for 5-LO and FLAP was similar in n ormal 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 cel l type in patients with cystic fibrosis whereas COX-1 levels in polymo rphs were similar to those in patients with asthma.Conclusions - The i ncreased leukotriene production in asthma and cystic fibrosis is not e xplained by an increase in transcription of 5-LO and FLAP. Transcripti on of 15-LO and COX-2 is increased in atopic asthma. Transcription of COX-1 is increased in both atopic asthma and cystic fibrosis.