5-Lipoxygenase products regulate basophil functions: 5-Oxo-ETE elicits migration, and leukotriene B(4) 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), LTD(4), 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 Ca(2+) mobilization, migration, CD 11b expression, and degranulation of human basophils. Expression of the receptors for LTC(4)/D(4)/E(4) (cysteinyl leukotriene 1 [CysLT(1)] and CysLT(2)), LTB4 (BLT(1) and BLT(2)), 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 BLT(2). 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 CysLT(1), CysLT(2), BLT(1), and OXE, but not BLT(2). All products elicited a transient increase of cytosolic calcium, with the order of magnitude being LTB(4)>5-oxo-ETE>LTD(4). 5-Oxo-ETE induced a strong basophil migratory response that was almost equivalent to that of prostaglandin D(2). LTB(4) elicited significant degranulation of IL-3-primed basophils. In contrast, no functional significance was observed for LTD(4).


CONCLUSIONS
Among 5-LO products, 5-oxo-ETE induces a potent basophil migratory response, and LTB(4) elicits degranulation under certain conditions. Our results strongly suggest that 5-oxo-ETE might afford opportunities for therapeutic targeting in allergic inflammation.
Iikura
Motoyasu
M
Department of Allergy and Rheumatology, University of Tokyo School of Medicine, Tokyo, Japan.
Suzukawa
Maho
M
Yamaguchi
Masao
M
Sekiya
Takashi
T
Komiya
Akiko
A
Yoshimura-Uchiyama
Chitose
C
Nagase
Hiroyuki
H
Matsushima
Kouji
K
Yamamoto
Kazuhiko
K
Hirai
Koichi
K
D001094:Arachidonate 5-Lipoxygenase / Q000276:immunology / Q000378:metabolism*; D001095:Arachidonic Acids / Q000276:immunology / Q000378:metabolism*; D015549:Basophil Degranulation Test; D001491:Basophils / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002630:Chemotactic Factors / Q000276:immunology / Q000378:metabolism; D015777:Eicosanoids / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007975:Leukotriene B4 / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018055:Receptors, Eicosanoid / Q000276:immunology / Q000378:metabolism; D018077:Receptors, Leukotriene / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001095:Arachidonic Acids; D002630:Chemotactic Factors; D015777:Eicosanoids; D012333:RNA, Messenger; D018055:Receptors, Eicosanoid; D018077:Receptors, Leukotriene; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; D007975:Leukotriene B4; D001094:Arachidonate 5-Lipoxygenase; D002118:Calcium