15-hydroxy-5-8-11-13-eicosatetraenoic-acid and Lung-Diseases--Obstructive

We evaluated the levels of 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE] and the expression of 15-lipoxygenase (15-LO) mRNA in induced sputum obtained from 10 control and 15 chronic bronchitis subjects. 15(S)-HETE was evaluated by reverse phase high-performance liquid chromatography separation followed by specific RIA. 15-LO mRNA expression was determined by primed in situ labeling. The levels of both soluble and cell-associated 15(S)-HETE resulted significantly higher in chronic bronchitis than in control subjects. The percentage of cells expressing 15-LO mRNA was significantly higher in chronic bronchitis than in control subjects (P < 0.01). Double staining for specific cell type markers and 15-LO mRNA showed macrophages and neutrophils positive for 15-LO, whereas similar staining of peripheral blood neutrophils did not show evidence for 15-LO expression, suggesting that expression of 15-LO in neutrophils takes place on migration into the airways. Because 15(S)-HETE inversely correlated with the percentage of neutrophils in sputum of chronic bronchitis subjects, we studied the effect of 15(S)-HETE on leukotriene B(4) (LTB(4)) production in vitro and evaluated the concentration of LTB(4) in induced sputum and the contribution of LTB(4) to the chemotactic activity of induced sputum samples ex vivo. The results obtained indicate that macrophages and neutrophils present within the airways of chronic bronchitis subjects express 15-LO mRNA; increased basal levels of 15(S)-HETE may contribute to modulate, through the inhibition of 5-lipoxygenase metabolites production, neutrophil infiltration and airway inflammation associated with chronic bronchitis.

Topics: Adult; Aged; Arachidonate 15-Lipoxygenase; Bronchitis; Cell Count; Cell Survival; Cells, Cultured; Chemotaxis, Leukocyte; Chronic Disease; Humans; Hydroxyeicosatetraenoic Acids; Immunohistochemistry; In Situ Hybridization; Ionophores; Leukotriene Antagonists; Leukotriene B4; Lung Diseases, Obstructive; Macrophages; Middle Aged; Neutrophils; RNA, Messenger; Sputum

Airway obstruction and hyperreactivity are characteristics of human asthma and of "heaves," a naturally occurring respiratory disorder of horses and ponies. We measured pulmonary function and plasma immunoreactive 15-hydroxyeicosatetraenoic acid (i15-HETE) concentrations in simultaneously collected carotid artery and right ventricle blood samples in five affected ponies and their age- and gender-matched control ponies. Measurements and sampling were performed before (Period A), during (Period B), and following recovery from (Period C) acute airway obstruction precipitated by housing ponies in a barn and exposing them to hay dust. Pulmonary resistance increased significantly, and dynamic compliance and PaO2 decreased significantly in affected ponies at Period B. Plasma i15-HETE concentrations were greater in carotid artery samples compared with right ventricle samples in affected ponies at each measurement period, suggesting that the lung was a source of i15-HETE. Carotid artery i15-HETE concentrations were significantly greater in affected ponies than in control ponies and increased at Period B. There was a significant negative correlation between changes in plasma i15-HETE and changes in dynamic compliance between measurement Periods A and B. We conclude that the lung is a source of i15-HETE in ponies with heaves, that these ponies produce greater quantities of i15-HETE than control ponies, and that exposing affected ponies to a barn environment produces acute airway obstruction and increased plasma concentrations of i15-HETE.

Topics: Animals; Asthma; Chromatography, High Pressure Liquid; Disease Models, Animal; Horse Diseases; Horses; Hydroxyeicosatetraenoic Acids; Lung; Lung Diseases, Obstructive; Radioimmunoassay; Respiratory Function Tests