A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection.
Suzuki, Hiroshi; Kurihara, Yukiko; Takeya, Motohiro; Kamada, Nobuo; Kataoka, Motoyuki; Jishage, Kouichi; Ueda, Otoya; Sakaguchi, Hisashi; Higashi, Takayuki; Suzuki, Tsukasa; Takashima, Yoshiaki; Kawabe, Yoshiki; Cynshi, Osamu; Wada, Youichiro; Honda, Makoto; Kurihara, Hiroki; Aburatani, Hiroyuki; Doi, Takefumi; Matsumoto, Akiyo; Azuma, Sadahiro; Noda, Tetsuo; Toyoda, Yutaka; Itakura, Hiroshige; Yazaki, Yoshio; Horiuchi, Seikoh; Takahashi, Kiyoshi; Kruijt, J. Kar; van Berkel, Theo J. C.; Steinbrecher, Urs P.; Ishibashi, Shun; Maeda, Nobuyo; Gordon, Siamon; Kodama; Tatsuhiko
[Letter]
Nature.
386(6622):292-296, March 20, 1997.
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Macrophage type-I and type-II class-A scavenger receptors (MSR-A) are implicated in the pathological deposition of cholesterol during atherogenesis as a result of receptor-mediated uptake of modified low-density lipoproteins (mLDL). MSR-A can bind an extraordinary wide range of ligands, including bacterial pathogens, and also mediates cation-independent macrophage adhesion in vitro. Here we show that targeted disruption of the MSR-A gene in mice results in a reduction in the size of atherosclerotic lesions in an animal deficient in apolipoprotein E. Macrophages from MSR-A-deficient mice show a marked decrease in mLDL uptake in vitro, whereas mLDL clearance from plasma occurs at a normal rate, indicating that there may be alternative mechanisms for removing mLDL from the circulation. In addition, MSR-A-knockout mice show an increased susceptibility to infection with Listeria monocytogenes or herpes simplex virus type-1, indicating that MSR-A may play a part in host defence against pathogens.
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