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: L M Kuitert, R Newton, N C Barnes, I M Adcock, P J Barnes
• Journal: Thorax (Thorax) Vol. 51 Issue 12 Pg. 1223-8 (Dec 1996) ISSN: 0040-6376 [Print] England
• PMID: 8994519 (Publication Type: Journal Article)

Chemical References

• 5-Lipoxygenase-Activating Proteins
• ALOX5AP protein, human
• Carrier Proteins
• Eicosanoids
• Isoenzymes
• Membrane Proteins
• Arachidonate 15-Lipoxygenase
• Arachidonate 5-Lipoxygenase
• Prostaglandin-Endoperoxide Synthases

Topics

• 5-Lipoxygenase-Activating Proteins
• Adult
• Arachidonate 15-Lipoxygenase (metabolism)
• Arachidonate 5-Lipoxygenase (metabolism)
• Asthma (immunology, metabolism)
• Carrier Proteins (metabolism)
• Cystic Fibrosis (immunology, metabolism)
• Eicosanoids (metabolism)
• Female
• Humans
• Isoenzymes (metabolism)
• Leukocytes, Mononuclear (enzymology, metabolism)
• Male
• Membrane Proteins (metabolism)
• Middle Aged
• Neutrophils (enzymology, metabolism)
• Polymerase Chain Reaction
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Transcription, Genetic