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(Journal of Leukocyte Biology. 2001;69:105-112.)
© 2001 by Society for Leukocyte Biology

Pivotal role of 5-lipoxygenase in the activation of human eosinophils: platelet-activating factor and interleukin-5 induce CD69 on eosinophils through the 5-lipoxygenase pathway

Tetsuya Urasaki^*, Jun Takasaki, Toshiro Nagasawa^* and Haruhiko Ninomiya

^* Division of Hematology, Institute of Clinical Medicine, University of Tsukuba
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.
College of Medical Technology, University of Tsukuba, Japan

Correspondence: Haruhiko Ninomiya, M.D., Ph.D., College of Medical Technology, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8577, Japan. E-mail: hninomiya{at}itan.tsukuba.ac.jp

CD69 is an activation-related cell surface molecule on human eosinophils. It has been reported that interleukin (IL)-5, but not platelet-activating factor (PAF), can induce CD69 on human eosinophils in vitro. In this study, PAF induced CD69 intensely on eosinophils from patients with hypereosinophilic syndrome (HES), while only weakly on those from normal donors. Because HES eosinophils contain abundant cytosolic phospholipase A₂ (cPLA₂) and 5-lipoxygenase (5-LO), we examined the roles of several enzymes involved in the metabolism of arachidonic acid in the PAF- or IL-5-induced CD69 expression on eosinophils. The CD69 expression induced by PAF and IL-5 on HES eosinophils and that by IL-5 on normal eosinophils were both inhibited by AA861 and MK-886, inhibitors of 5-LO activity. In addition, AACOCF₃, a selective cPLA₂ inhibitor, inhibited IL-5-induced CD69 expression on normal eosinophils, although it hardly affected either IL-5- or PAF-induced CD69 expression on HES eosinophils. Moreover, PAF alone induced CD69 only weakly on normal eosinophils, but exogenous arachidonic acid remarkably enhanced PAF-induced CD69 expression on them. These findings suggest that IL-5 activates both cPLA₂ and 5-LO but PAF activates only 5-LO. It is suggested that 5-LO plays a critical role in the induction of CD69 on eosinophils.

Key Words: hypereosinophilic syndrome • cytosolic phospholipase A₂ • arachidonic acid

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