Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 42, Issue 5, Pages 654-664Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2006.12.006
Keywords
5-HETE; 5-hydroxyeicosanoid dehydrogenase; 5-lipoxygenase products; 5-oxo-ETE; airway epithelial cells; airway smooth muscle cells; eicosanoids; glutathione; hydrogen peroxide; inflammation; NADP(+)
Funding
- NHLBI NIH HHS [HL69835, HL81873, R01 HL069835, R01 HL081873] Funding Source: Medline
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5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is a potent eosinophil chemoattractant that is synthesized from the 5-lipoxygenase product 5S-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) by the NADP(+)-dependent enzyme 5-hydroxycicosanoid dehydrogenase (5-HEDH), previously reported only in inflammatory cells. Because of their critical location at the interface of the lung with the external environment, we sought to determine whether epithelial cells could also synthesize this substance. We found that HEp-2, T84, A549, and BEAS-2B cells all synthesize 5-oxo-ETE from 5-HETE in amounts comparable to leukocytes. The epithelial dehydrogenase is localized in the microsomal fraction, requires NADP(+), and is selective for the S-isomer of 5-HETE, suggesting that it is identical to leukocyte 5-HEDH. Normal human bronchial epithelial cells have An even greater capacity to synthesize 5-oxo-ETE. H2O2 dramatically stimulates its synthesis in association with increased levels of intracellular GSSG and NADP(+). These responses were all blocked by removal of GSH/GSSG with N-ethylmaleimide, suggesting that H2O2 stimulates 5-oxo-ETE synthesis by raising NADP+ levels through activation of the GSH redox cycle. Airway smooth muscle cells can also synthesize 5-oxo-ETE, but to a lesser extent. These results suggest that epithelial cells may be a major source of 5-oxo-ETE under conditions of oxidative stress, which may contribute to eosinophil infiltration in allergic diseases. (c) 2006 Elsevier Inc. All rights reserved.
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