Expression and activation of 15-lipoxygenase pathway in severe asthma: relationship to eosinophilic phenotype and collagen deposition.
BACKGROUND
Although 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), a product of 15-lipoxygenase (15-LO), may be involved in mild to moderate asthma, little is known about its potential roles in severe asthma.


OBJECTIVE
This study was performed to evaluate 15(S)-HETE levels in bronchoalveolar lavage fluid (BALF) from severe asthmatics with and without airway eosinophils and from the control groups. In addition, 15-LO protein expression was examined in endobronchial biopsy, while its expression and activation were evaluated in BAL cells.


RESULTS
While 15(S)-HETE levels in BALF were significantly higher in all severe asthmatics than normal subjects, severe asthmatics with airway eosinophils had the highest levels compared with mild, moderate asthmatics and normal subjects. 15(S)-HETE levels were associated with tissue eosinophil numbers, sub-basement membrane thickness and BALF tissue inhibitor of metalloproteinase-1 levels, and were accompanied by increased 15-LO expression in bronchial epithelium. In addition, activation of 15-LO was suggested by the increased proportion of 15-LO in the cytoplasmic membrane of alveolar macrophages from severe asthmatics.


CONCLUSIONS
The data suggest that severe asthmatics with persistent airway eosinophils manifest high levels of 15(S)-HETE in BALF, which may be associated with airway fibrosis. It is likely that 15-LO expression and activation by airway cells explain the increased 15(S)-HETE levels.
Chu
H W
HW
Department of Medicine, National Jewish Medical and Research Center, 1400 Jackson Street, D104, Denver 80206, Colorado, USA. chuhw@njc.org
Balzar
S
S
Westcott
J Y
JY
Trudeau
J B
JB
Sun
Y
Y
Conrad
D J
DJ
Wenzel
S E
SE
D000328:Adult; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D003094:Collagen / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D005355:Fibrosis; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000502:physiology*
D006893:Hydroxyeicosatetraenoic Acids; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D003094:Collagen; D001093:Arachidonate 15-Lipoxygenase