5-Lipoxygenase products regulate basophil functions:: 5-Oxo-ETE elicits migration, and leukotriene B4 induces degranulation

Background: 5-Lipoxygenase (5-LO) products have been strongly implicated in the pathogenesis of allergic diseases. In addition to their physiologic effects on residential cells, 5-LO products are capable of stimulating various eosinophil functions. However, little is known regarding the effects of 5-LO products on basophil functions. Objective: This study was designed to elucidate the effects of the main 5-LO products (ie, leukotriene [LT] B-4, LTD4, and 5-oxo-6,8,11,14-eicosatetraenoic acid [5-oxo-ETE]), as well as their receptor expression on human basophils. Methods: We studied the effects of 5-LO products on Ca2+ mobilization, migration, CD11b expression, and degranulation of human basophils. Expression of the receptors for LTC4/D-4/ E-4 (cysteinyl leukotriene 1 [CysLT(1)] and CysLT(2)), LTB4 (BLT1 and BLT2), and 5-oxo-ETE (oxoeicosanoid [OXE]) was assessed by means of real-time PCR and flow cytometry. Results: At the mRNA level, basophils strongly expressed OXE and predominantly expressed CysLT(1) and BLT2. The expression level of OXE mRNA in basophils was approximately 20-fold higher than in neutrophils and similar to that in eosinophils. At the protein level, basopbils expressed CysLT(1), CysLT(2), BLT1, and OXE, but not BLT2. All products elicited a transient increase of cytosolic calcium, with the order of magnitude being LTB4 > 5-oxo-ETE > LTD4. 5-Oxo-ETE induced a strong basophil migratory response that was almost equivalent to that of prostaglandin D-2. LTB4 elicited significant degranulation of IL-3-primed basophils. In contrast, no functional significance was observed for LTD4. Conclusion: Among 5-LO products, 5-oxo-FTE induces a potent basophil migratory response, and LTB4 elicits degranulation under certain conditions. Our results strongly suggest that 5-oxo-ETE might afford opportunities for therapeutic targeting in allergic inflammation.