Immunoglobulin treatment suppresses atherosclerosis in apolipoprotein E-deficient mice via the Fc portion
1 Department of Cardiovascular Medicine and 2 Department of Geriatric Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan Submitted 28 October 2002 ; accepted in final form 24 March 2003 Atherosclerosis is associated with immune activation. Immunoglobulin is used for the t...
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Published in | American journal of physiology. Heart and circulatory physiology Vol. 285; no. 2; pp. H899 - H906 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.08.2003
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Subjects | |
Online Access | Get full text |
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Summary: | 1 Department of Cardiovascular Medicine and
2 Department of Geriatric Medicine, Graduate School of
Medicine, Kyoto University, Kyoto 606-8507, Japan
Submitted 28 October 2002
; accepted in final form 24 March 2003
Atherosclerosis is associated with immune activation. Immunoglobulin is
used for the treatment of immune-mediated diseases. The mechanisms and
importance of the Fc portion of immunoglobulin upon experimental
atherosclerosis in apolipoprotein E-deficient mice were examined. Experimental
atherosclerosis was induced in mice fed a high-fat diet containing 0.3%
cholesterol. Over 8, 12, and 16 wk, on alternate days, mice were treated with
an intraperitoneal injection of either 1
g·kg 1 ·day 1
of human intact immunoglobulin or F(ab') 2 fragments of human
immunoglobulin. Fatty streak formation and fibrofatty plaques were markedly
suppressed in mice that received intact immunoglobulin for 8, 12, and 16 wk.
In contrast, atherosclerotic lesions were not ameliorated in mice that
received F(ab') 2 fragments. Immunohistochemical analysis
revealed that macrophage accumulation in the fatty streak lesions was
suppressed in mice received intact immunoglobulin but not in those that
received F(ab') 2 fragments. In addition, the cytotoxic
activities of splenocytes from immunoglobulin-treated mice, but not from
F(ab') 2 fragment-treated mice, were significantly suppressed
compared with those from human serum albumin-treated mice. Differences in
lesion area did not correlate with any significant alterations in serum lipid
levels. Immunoglobulin therapy markedly suppressed atherosclerosis due to Fc
receptor-mediated anti-inflammatory and immunomodulating actions. The
antiatherosclerotic effects of immunoglobulin may be related to the
suppression of cytotoxic activity of atherogenic T cells and the reduction of
macrophage accumulation in the lesions.
knockout mice; Fc receptor
Address for reprint requests and other correspondence: C. Kishimoto, Dept. of
Cardiovascular Medicine, Graduate School of Medicine, Kyoto Univ., 54
Kawaracho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan (E-mail:
kkishi{at}kuhp.kyoto-u.ac.jp ). |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0363-6135 1522-1539 |
DOI: | 10.1152/ajpheart.00926.2002 |