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

2005; Elsevier BV; Volume: 116; Issue: 3 Linguagem: Inglês

10.1016/j.jaci.2005.04.029

1097-6825

Motoyasu Iikura, Maho Suzukawa, Masao Yamaguchi, Takashi Sekiya, Akiko Komiya, Chitose Yoshimura-Uchiyama, Hiroyuki Nagase, Kouji Matsushima, Kazuhiko Yamamoto, Koichi Hirai,

Urticaria and Related Conditions

Background5-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.ObjectiveThis study was designed to elucidate the effects of the main 5-LO products (ie, leukotriene [LT] B4, LTD4, and 5-oxo-6,8,11,14-eicosatetraenoic acid [5-oxo-ETE]), as well as their receptor expression on human basophils.MethodsWe studied the effects of 5-LO products on Ca2+ mobilization, migration, CD11b expression, and degranulation of human basophils. Expression of the receptors for LTC4/D4/E4 (cysteinyl leukotriene 1 [CysLT1] and CysLT2), LTB4 (BLT1 and BLT2), and 5-oxo-ETE (oxoeicosanoid [OXE]) was assessed by means of real-time PCR and flow cytometry.ResultsAt the mRNA level, basophils strongly expressed OXE and predominantly expressed CysLT1 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, basophils expressed CysLT1, CysLT2, 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 D2. LTB4 elicited significant degranulation of IL-3–primed basophils. In contrast, no functional significance was observed for LTD4.ConclusionAmong 5-LO products, 5-oxo-ETE 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.