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(Journal of Leukocyte Biology. 2001;69:732-740.)
© 2001 by Society for Leukocyte Biology

Mixed allogeneic chimerism with wild-type strains ameliorates atherosclerosis in apolipoprotein E-deficient mice

Naoki Ishimori^*,, Kazuya Iwabuchi^*, Satoshi Fujii, Keiko Watano^*,, Chikako Iwabuchi^*, Manabu Ato^*, Hitoshi Chiba, Shinya Tanaka, Akira Kitabatake and Kazunori Onoé^*

^* Division of Immunobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, and Departments of
Cardiovascular Medicine,
Laboratory Medicine, and
Molecular and Cellular Pathology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

Correspondence: Kazunori Onoé, Division of Immunobiology, Research Section of Pathophysiology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan. E-mail: kazunori{at}imm.hokudai.ac.jp

Atherosclerosis involves inflammatory processes between vascular tissues and hematocytes with a hyperlipidemic background. To examine whether variations of hematocytes constitute one of the genetic components in atherosclerosis, irradiated apolipoprotein E (apoE)-deficient (apoE^-/-) mice with hypercholesterolemia and preexisting atherosclerotic lesions were reconstituted with mixed bone marrow cells (BMC) from syngeneic and wild-type (apoE^+/+; atherosclerosis-resistant SJL or -susceptible B10.S) mice. Stable mixed allogeneic chimeras with small amounts of serum apoE were established without any detrimental complications. Compared with untreated apoE^-/- mice or apoE^-/- mice transplanted with syngeneic BMC alone, significant reduction of the cholesterol level and significant lesion regression were observed in the mixed chimeras. Furthermore, mixed chimeras given SJL BMC showed marked reductions in numbers of lesions compared with those reconstituted with B10.S BMC. Cholesterol levels in the former SJL chimeras, however, were significantly higher than those in the latter B10.S chimeras. These findings indicate that the resistance of SJL to atherosclerosis resides in the bone marrow-derived cells.

Key Words: bone marrow transplantation • bone marrow-derived cell • gene transfer • hypercholesterolemia • inbred strains • macrophage

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