title: Expression and function of cystine/glutamate transporter in neutrophils.
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.
authors.affiliation: Department of Biochemistry, Institute of Basic Medical Science, University of Tsukuba, Ibaraki, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sakakura
authors.forename: Hideyo
authors.initials: H
authors.lastname: Sato
authors.forename: Ayako
authors.initials: A
authors.lastname: Shiiya
authors.forename: Michiko
authors.initials: M
authors.lastname: Tamba
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Sagara
authors.forename: Manabu
authors.initials: M
authors.lastname: Matsuda
authors.forename: Naomichi
authors.initials: N
authors.lastname: Okamura
authors.forename: Nobuo
authors.initials: N
authors.lastname: Makino
authors.forename: Shiro
authors.initials: S
authors.lastname: Bannai
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D027182:Amino Acid Transport System y+ / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D003553:Cystine / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism*; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism; D013481:Superoxides / Q000097:blood / Q000378:metabolism
chemical_list: D027322:Amino Acid Transport System X-AG; D027182:Amino Acid Transport System y+; D013481:Superoxides; D003553:Cystine; D005978:Glutathione