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Fc{gamma}RIIB Inhibits the Development of Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice.

Zhao, Ming LU ; Wigren, Maria LU ; Dunér, Pontus LU ; Kolbus, Daniel LU ; Berg, Katarina LU ; Björkbacka, Harry LU ; Nilsson, Jan LU and Nordin Fredrikson, Gunilla LU (2010) In Journal of Immunology 184(5). p.2253-2260
Abstract
The immune processes associated with atherogenesis have received considerable attention during recent years. IgG FcRs (FcgammaR) are involved in activating the immune system and in maintaining peripheral tolerance. However, the role of the inhibitory IgG receptor FcgammaRIIB in atherosclerosis has not been defined. Bone marrow cells from FcgammaRIIB-deficient mice and C57BL/6 control mice were transplanted to low-density lipoprotein receptor-deficient mice. Atherosclerosis was induced by feeding the recipient mice a high-fat diet for 8 wk and evaluated using Oil Red O staining of the descending aorta at sacrifice. The molecular mechanisms triggering atherosclerosis was studied by examining splenic B and T cells, as well as Th1 and Th2... (More)
The immune processes associated with atherogenesis have received considerable attention during recent years. IgG FcRs (FcgammaR) are involved in activating the immune system and in maintaining peripheral tolerance. However, the role of the inhibitory IgG receptor FcgammaRIIB in atherosclerosis has not been defined. Bone marrow cells from FcgammaRIIB-deficient mice and C57BL/6 control mice were transplanted to low-density lipoprotein receptor-deficient mice. Atherosclerosis was induced by feeding the recipient mice a high-fat diet for 8 wk and evaluated using Oil Red O staining of the descending aorta at sacrifice. The molecular mechanisms triggering atherosclerosis was studied by examining splenic B and T cells, as well as Th1 and Th2 immune responses using flow cytometry and ELISA. The atherosclerotic lesion area in the descending aorta was approximately 5-fold larger in mice lacking FcgammaRIIB than in control mice (2.75 +/- 2.57 versus 0.44 +/- 0.42%; p < 0.01). Moreover, the FcgammaRIIB deficiency resulted in an amplified splenocyte proliferative response to Con A stimulation (proliferation index 30.26 +/- 8.81 versus 2.96 +/- 0.81%, p < 0.0001) and an enhanced expression of MHC class II on the B cells (6.65 +/- 0.64 versus 2.33 +/- 0.25%; p < 0.001). In accordance, an enlarged amount of CD25-positive CD4 T cells was found in the spleen (42.74 +/- 4.05 versus 2.45 +/- 0.31%; p < 0.0001). The plasma Ab and cytokine pattern suggested increased Th1 and Th2 immune responses, respectively. These results show that FcgammaRIIB inhibits the development of atherosclerosis in mice. In addition, they indicate that absence of the inhibiting IgG receptor cause disease, depending on an imbalance of activating and inhibiting immune cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
184
issue
5
pages
2253 - 2260
publisher
American Association of Immunologists
external identifiers
  • wos:000274768900006
  • pmid:20097865
  • scopus:77951906484
ISSN
1550-6606
DOI
10.4049/jimmunol.0902654
language
English
LU publication?
yes
id
8f20a1c0-8fa2-43ee-9edd-e8f6084948d2 (old id 1540635)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20097865?dopt=Abstract
date added to LUP
2010-02-03 10:44:46
date last changed
2018-07-15 03:51:33
@article{8f20a1c0-8fa2-43ee-9edd-e8f6084948d2,
  abstract     = {The immune processes associated with atherogenesis have received considerable attention during recent years. IgG FcRs (FcgammaR) are involved in activating the immune system and in maintaining peripheral tolerance. However, the role of the inhibitory IgG receptor FcgammaRIIB in atherosclerosis has not been defined. Bone marrow cells from FcgammaRIIB-deficient mice and C57BL/6 control mice were transplanted to low-density lipoprotein receptor-deficient mice. Atherosclerosis was induced by feeding the recipient mice a high-fat diet for 8 wk and evaluated using Oil Red O staining of the descending aorta at sacrifice. The molecular mechanisms triggering atherosclerosis was studied by examining splenic B and T cells, as well as Th1 and Th2 immune responses using flow cytometry and ELISA. The atherosclerotic lesion area in the descending aorta was approximately 5-fold larger in mice lacking FcgammaRIIB than in control mice (2.75 +/- 2.57 versus 0.44 +/- 0.42%; p &lt; 0.01). Moreover, the FcgammaRIIB deficiency resulted in an amplified splenocyte proliferative response to Con A stimulation (proliferation index 30.26 +/- 8.81 versus 2.96 +/- 0.81%, p &lt; 0.0001) and an enhanced expression of MHC class II on the B cells (6.65 +/- 0.64 versus 2.33 +/- 0.25%; p &lt; 0.001). In accordance, an enlarged amount of CD25-positive CD4 T cells was found in the spleen (42.74 +/- 4.05 versus 2.45 +/- 0.31%; p &lt; 0.0001). The plasma Ab and cytokine pattern suggested increased Th1 and Th2 immune responses, respectively. These results show that FcgammaRIIB inhibits the development of atherosclerosis in mice. In addition, they indicate that absence of the inhibiting IgG receptor cause disease, depending on an imbalance of activating and inhibiting immune cells.},
  author       = {Zhao, Ming and Wigren, Maria and Dunér, Pontus and Kolbus, Daniel and Berg, Katarina and Björkbacka, Harry and Nilsson, Jan and Nordin Fredrikson, Gunilla},
  issn         = {1550-6606},
  language     = {eng},
  number       = {5},
  pages        = {2253--2260},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Fc{gamma}RIIB Inhibits the Development of Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice.},
  url          = {http://dx.doi.org/10.4049/jimmunol.0902654},
  volume       = {184},
  year         = {2010},
}