Journal of Leukocyte Biology eBioscience full spectrum cell analysis
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A more recent version of this article appeared on April 1, 2007

Published online before print January 2, 2007
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0606385

Received for publication June 9, 2006.
Revised November 2, 2006.
Accepted for publication December 1, 2006.

Article

Expression and function of cystine/glutamate transporter in neutrophils

Yuki Sakakura *{dagger}, Hideyo Sato {ddagger}@, Ayako Shiiya *, Michiko Tamba *, Jun-ichi Sagara {sect}, Manabu Matsuda *, Naomichi Okamura *, Nobuo Makino {dagger}, and Shiro Bannai *

*Department of Biochemistry, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan; {ddagger}Department of Bioresource Engineering, Faculty of Agriculture, Yamagata University, Tsuruoka, Yamagata, Japan; and Centers for {sect}Medical Science and {dagger}Humanity and Health Sciences, Ibaraki Prefectural University of Health Sciences, Ami, Ibaraki, Japan

@ To whom correspondence should be addressed. E-mail: shideyo{at}tds1.tr.yamagata-u.ac.jp.


  Abstract

Reactive oxygen species (ROS) produced by neutrophils are essential in the host defense against infections but may be harmful to neutrophils themselves. Glutathione (GSH) plays a pivotal role in protecting cells against ROS-mediated oxidant injury. Cystine/glutamate transporter, designated as system xc- and consisting of two proteins, xCT and 4F2hc, is important to maintain GSH levels in mammalian-cultured cells. In the present paper, we have investigated system xc- in neutrophils. In human peripheral blood neutrophils, neither the activity of system xc- nor xCT mRNA was detected. The activity was induced, and xCT mRNA was expressed when they were cultured in vitro. The mRNA expression was much enhanced in the presence of opsonized zymosan or PMA. In contrast, mouse peritoneal exudate neutrophils, immediately after preparation, exhibited system xc- activity and expressed xCT mRNA. The activity and the expression were heightened further when they were cultured. Peritoneal exudate cells (mostly neutrophils) from xCT-deficient (xCT-/-) mice had lower cysteine content than those from the wild-type mice. GSH levels in the xCT-/-cells decreased rapidly when they were cultured, whereas those in the wild-type cells were maintained during the culture. Apoptosis induced in culture was enhanced in the xCT-/- cells compared with the wild-type cells. These results suggest that system xc- plays an important role in neutrophils when they are activated, and their GSH consumption is accelerated.

Key Words: glutathione • redox • superoxide • apoptosis






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