title: Xenogenic macrophage immunization reduces atherosclerosis in apolipoprotein E knockout mice.
abstract: 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.
authors.affiliation: 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. tomoya@med.kobe-u.ac.jp
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yamashita
authors.forename: Seinosuke
authors.initials: S
authors.lastname: Kawashima
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Hirase
authors.forename: Masakazu
authors.initials: M
authors.lastname: Shinohara
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Takaya
authors.forename: Naoto
authors.initials: N
authors.lastname: Sasaki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takeda
authors.forename: Hideto
authors.initials: H
authors.lastname: Tawa
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Inoue
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokoyama
mesh_terms: D034841:Abdominal Cavity; D000818:Animals; D000910:Antibodies, Heterophile / Q000276:immunology; D015478:Antigens, Heterophile / Q000276:immunology*; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D005260:Female; D006801:Humans; D007114:Immunization; D007167:Immunotherapy / Q000379:methods*; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology
chemical_list: D000910:Antibodies, Heterophile; D015478:Antigens, Heterophile; D001057:Apolipoproteins E; D016753:Interleukin-10; D018664:Interleukin-12