Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9034487 | Toxicology | 2005 | 9 Pages |
Abstract
This study was designed to investigate bactericidal activity of and nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated peritoneal exudate macrophages (MÏ) from metallothionein (MT)-null mice. Control MÏ had a bactericidal effect on Staphylococcus aureus, but MT-null MÏ had significantly lower activity. NO is an important factor in the bactericidal function of MÏ. LPS-stimulated MT-null MÏ produced less NO than those of control mice. LPS-stimulated MÏ produce cytokines such as tumor necrosis factor (TNF)-alpha. TNF-alpha activate MÏ and stimulates NO production. We evaluated NO production by TNF-alpha-stimulated MÏ. MT-null MÏ produced less NO in response to TNF-alpha stimulation. Levels of expression of inducible NO synthase (iNOS) mRNA and production of iNOS protein in response to LPS stimulation were similar in MT-null and control cells, as were levels of expression of arginase, which competes in arginine metabolism with iNOS. No notable changes were found in arginine uptake or in expression of cationic amino acid transporter 2 (a major arginine transporter in MÏ) between control and MT-null MÏ. The rate of conversion of [14C]-l-arginine to citrulline, which is formed with NO by the action of iNOS, was much lower in MT-null MÏ than in control cells. These results indicate that the reduced production of NO in MT-deficient MÏ is due mainly to reduced activity of iNOS. Thus, MT plays important roles in bactericidal activity, NO production, and arginine metabolism in activated MÏ.
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Authors
Norio Itoh, Hiroshi Shibayama, Masako Kanekiyo, Dunkokkuruad Namphung, Tsuyoshi Nakanishi, Akiko Matsuyama, Tomoyuki Odani, Keiichi Tanaka,