15(S)-HETE modulates LTB(4) production and neutrophil chemotaxis in chronic bronchitis.
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.
Profita
M
M
Istituto di Fisiopatologia Respiratoria, Consiglio Nazionale delle Ricerche, Palermo, Italy.
Sala
A
A
Riccobono
L
L
Pace
E
E
Paternò
A
A
Zarini
S
S
Siena
L
L
Mirabella
A
A
Bonsignore
G
G
Vignola
A M
AM
D000328:Adult; D000368:Aged; D001093:Arachidonate 15-Lipoxygenase / Q000096:biosynthesis / Q000235:genetics; D001991:Bronchitis / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002908:Chronic Disease; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007476:Ionophores / Q000494:pharmacology; D020024:Leukotriene Antagonists / Q000494:pharmacology; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008173:Lung Diseases, Obstructive / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D013183:Sputum / Q000737:chemistry / Q000166:cytology / Q000378:metabolism
D006893:Hydroxyeicosatetraenoic Acids; D007476:Ionophores; D020024:Leukotriene Antagonists; D012333:RNA, Messenger; D007975:Leukotriene B4; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001093:Arachidonate 15-Lipoxygenase