Expression and activation of 15‐lipoxygenase pathway in severe asthma: relationship to eosinophilic phenotype and collagen deposition

Abstract

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.

IgE expression pattern in lung: Relation to systemic IgE and asthma phenotypes

“…Interestingly, although anti-IgE therapy significantly decreased eosinophilic inflammation and tissue and serum IgE levels, these changes did not improve lung function 3 . While these complex but consistent relationships suggest that increased IgE binding to mast cells and concomitant acute reactions are marginally related to very severe exacerbations, the relation of mast cell IgE to lung function also suggests that persistent engagement of Th2 pathways in asthma may preserve airflow through reparative/pro-fibrotic effects 15,[33][34][35] Although analyzing human tissue samples offers indispensable information about the in vivo tissue environment, conclusions about the causality of the processes cannot be made. Also, this study did not evaluate the presence of IgE-producing plasma cells in the submucosa.…”

Eoxins are proinflammatory arachidonic acid metabolites produced via the 15-lipoxygenase-1 pathway in human eosinophils and mast cells

“…Human tracheal epithelial cells, chopped human bronchi, and human lung homogenates convert arachidonic acid mainly to 15-HETE (5,12). Lung specimens from asthmatic subjects produce more 15-HETE than specimens from nonasthmatic subjects (13)(14)(15). Increased amounts of 15-HETE have been found in bronchoalveolar lavage fluid (BALF) of antigenchallenged atopic asthmatic patients (16), in sputum samples from asthmatic subjects (17), and in nasal secretions from healthy control subjects (18).…”

“…Increased amounts of 15-HETE have been found in bronchoalveolar lavage fluid (BALF) of antigenchallenged atopic asthmatic patients (16), in sputum samples from asthmatic subjects (17), and in nasal secretions from healthy control subjects (18). Severely asthmatic patients with persistent airway eosinophilia have higher levels of 15-HETE in BALF compared with healthy subjects or with patients with asthma but without eosinophilia (14). The levels of 15-HETE correlate with subbasement membrane thickness, indicating that 15-LO might be associated with airway remodeling (14).…”

“…Severely asthmatic patients with persistent airway eosinophilia have higher levels of 15-HETE in BALF compared with healthy subjects or with patients with asthma but without eosinophilia (14). The levels of 15-HETE correlate with subbasement membrane thickness, indicating that 15-LO might be associated with airway remodeling (14).…”

“…15(S)-HETE is formed from 15(S)-hydroperoxy-eicosatetraenoic acid [15(S)-HPETE], and, in addition to undergoing reduction to 15-HETE, 15-HPETE may also undergo dehydration to form 14,15-epoxy-eicosatetraenoic acid (14, ) (19,20). Another 15-LO-1-derived metabolite, 5-oxo-15-hydroxy-6,8,11,13-eicosatetraenoic acid, produced by eosinophils, has been reported to be a potent chemotactic agent for human eosinophils (21).…”