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Am J Physiol Cell Physiol 293: C865-C873, 2007. First published June 6, 2007; doi:10.1152/ajpcell.00117.2007
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VASCULAR BIOLOGY

Xenogenic macrophage immunization reduces atherosclerosis in apolipoprotein E knockout mice

Tomoya Yamashita, Seinosuke Kawashima, Tetsuaki Hirase, Masakazu Shinohara, Tomofumi Takaya, Naoto Sasaki, Masafumi Takeda, Hideto Tawa, Nobutaka Inoue, Ken-ichi Hirata, and Mitsuhiro Yokoyama

Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan

Submitted 25 March 2007 ; accepted in final form 3 June 2007

Atherosclerosis is a complex chronic inflammatory disease in which macrophages play a critical role, and the intervention of the inflammatory process in atherogenesis could be a therapeutic strategy. In this study, we investigated the efficacy of xenogenic macrophage immunization on the atherosclerotic lesion formation in a model of murine atherosclerosis. Apolipoprotein E knockout (apoE-KO) mice were repeatedly immunized with formaldehyde-fixed cultured human macrophages (phorbol ester-stimulated THP-1 cells), using human serum albumin as a control protein or HepG2 cells as human control cells, once a week for four consecutive weeks. The vehicle phosphate-buffered saline was injected in the nonimmunized controls. THP-1 immunization induced antibodies that are immunoreactive with mouse macrophages. Although the plasma lipid levels were unchanged by the immunization, the atherosclerotic lesion area in the aortic root was significantly reduced by >50% in 16-wk-old THP-1-immunized apoE-KO mice compared with that in control mice. THP-1 immunization reduced in vivo macrophage infiltration, reduced in vitro macrophage adhesion, and changed cytokine production by macrophages to the antiatherogenic phenotype. Xenogenic macrophage immunization protects against the development of atherosclerosis in apoE-KO mice by modulating macrophage function in which antibodies induced by the immunization are likely to be involved. This method is a novel and potentially useful cell-mediated immune therapeutic technique against atherosclerosis.

antibody; THP-1 cells


Address for reprint requests and other correspondence: T. Yamashita, Division of Cardiovascular Medicine, Dept. of Internal Medicine, Kobe Univ. Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan (e-mail: tomoya{at}med.kobe-u.ac.jp)






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