5-Lipoxygenase products regulate basophil functions: 5-Oxo-ETE elicits migration, and leukotriene B4 induces degranulation - 18/08/11
, Maho Suzukawa, MD a, , Masao Yamaguchi, MD, PhD a, Takashi Sekiya, MD, PhD a, Akiko Komiya, MD, PhD a, Chitose Yoshimura-Uchiyama, MD, PhD a, Hiroyuki Nagase, MD, PhD a, Kouji Matsushima, MD, PhD b, Kazuhiko Yamamoto, MD, PhD a, Koichi Hirai, MD, PhD c, ⁎ 
Reprint requests: Koichi Hirai, MD, PhD, Department of Bioregulatory Function, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.Tokyo, Japan
Abstract |
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] B4, 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/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.
Results |
At 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.
Conclusion |
Among 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.
Le texte complet de cet article est disponible en PDF.Key words : Basophils, leukotriene D4, leukotriene B4, 5-oxo-6,8,11,14-eicosatetraenoic acid, receptor, CD11b, chemotaxis, degranulation, Ca2+ influx, human
Abbreviations used : CysLT, ED50, 5-LO, LT, MACS, OXE, 5-Oxo-ETE, PAF, PG
Plan
| Supported by a grant from the Ministry of Education, Science, Sports and Culture of Japan, and grants-in-aid from the Ministry of Health, Labor and Welfare of Japan. |
Vol 116 - N° 3
P. 578-585 - septembre 2005 Retour au numéro
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