A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection

Hiroshi Suzuki, Yukiko Kurihara, Motohiro Takeya, Nobuo Kamada, Motoyukl Kataoka, Kouichi Jishage, Otoya Ueda, Hisashl Sakaguchi, Takayuki Higashi, Tsukasa Suzuki, Yoshiaki Takashima, Yoshiki Kawabe, Osamu Cynshi, Youichiro Wada, Makoto Honda, Hiroki Kurihara, Hiroyuki Aburatani, Takefumi Doi, Akiyo Matsumoto, Sadahiro Azuma, Tetsuo Noda, Yutaka Toyoda, Hiroshige Itakura, Yoshio Yazaki, Seikoh Horiuchi, Kiyoshi Takahashi, J. Kar Kruijt, Theo J. C. van Berkel, Urs P. Steinbrecher, Shun Ishibashi, Nobuyo Maeda, Siamon Gordon and Tatsuhiko Kodama
Additional contact information
Hiroshi Suzuki: Chugai Pharmaceutical Co. Ltd
Yukiko Kurihara: University of Tokyo
Motohiro Takeya: Kumamoto University School of Medicine
Nobuo Kamada: Chugai Pharmaceutical Co. Ltd
Motoyukl Kataoka: CSK Research Park Inc.
Kouichi Jishage: Chugai Pharmaceutical Co. Ltd
Otoya Ueda: Chugai Pharmaceutical Co. Ltd
Hisashl Sakaguchi: Kumamoto University School of Medicine
Takayuki Higashi: Kumamoto University School of Medicine
Tsukasa Suzuki: Chugai Pharmaceutical Co. Ltd
Yoshiaki Takashima: Chugai Pharmaceutical Co. Ltd
Yoshiki Kawabe: Chugai Pharmaceutical Co. Ltd
Osamu Cynshi: Chugai Pharmaceutical Co. Ltd
Youichiro Wada: University of Tokyo
Makoto Honda: University of Tokyo
Hiroki Kurihara: University of Tokyo
Hiroyuki Aburatani: University of Tokyo
Takefumi Doi: Osaka University
Akiyo Matsumoto: National Institute of Health and Nutrition
Sadahiro Azuma: The University of Tokyo
Tetsuo Noda: Cancer Institute
Yutaka Toyoda: Obihiro University of Agriculture and Veterinary Medicine
Hiroshige Itakura: National Institute of Health and Nutrition
Yoshio Yazaki: University of Tokyo
Seikoh Horiuchi: Kumamoto University School of Medicine
Kiyoshi Takahashi: Kumamoto University School of Medicine
J. Kar Kruijt: Leiden University
Theo J. C. van Berkel: Leiden University
Urs P. Steinbrecher: University of British Columbia
Shun Ishibashi: University of Tokyo
Nobuyo Maeda: School of Medicine, University of North Carolina
Siamon Gordon: University of Oxford
Tatsuhiko Kodama: Research Center for Advanced Science and Technology, University of Tokyo

Nature, 1997, vol. 386, issue 6622, 292-296

Abstract: Abstract 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)1–6. MSR-A can bind an extraordinarily wide range of ligands, including bacterial pathogens7, and also mediates cation-independent macrophage adhesion in vitro8. 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.

Date: 1997
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DOI: 10.1038/386292a0

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