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BAFF receptor mAb treatment ameliorates development and progression of atherosclerosis in hyperlipidemic ApoE(-/-) mice
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 2832791
Author(s) Kyaw, T.; Cui, P.; Tay, C.; Kanellakis, P.; Hosseini, H.; Liu, E.; Rolink, A. G.; Tipping, P.; Bobik, A.; Toh, B. H.
Author(s) at UniBasel Rolink, Antonius G.
Year 2013
Title BAFF receptor mAb treatment ameliorates development and progression of atherosclerosis in hyperlipidemic ApoE(-/-) mice
Journal PLoS ONE
Volume 8
Number 4
Keywords Animals; Antibodies, Monoclonal/immunology/ pharmacology; Antigens, CD/genetics/immunology; Apolipoproteins E/ deficiency/genetics/immunology; Atherosclerosis/complications/ drug therapy/immunology/pathology; B-Cell Activation Factor Receptor/antagonists & inhibitors/genetics/immunology; B-Lymphocyte Subsets/ drug effects/immunology/pathology; Cytokines/biosynthesis/immunology; Diet, High-Fat; Disease Progression; Hyperlipidemias/complications/ drug therapy/immunology/pathology; Lymphocyte Depletion; Male; Mice; Mice, Knockout; Spleen/ drug effects/immunology/pathology
Abstract AIMS: Option to attenuate atherosclerosis by depleting B2 cells is currently limited to anti-CD20 antibodies which deplete all B-cell subtypes. In the present study we evaluated the capacity of a monoclonal antibody to B cell activating factor-receptor (BAFFR) to selectively deplete atherogenic B2 cells to prevent both development and progression of atherosclerosis in the ApoE(-/-) mouse. METHODS AND RESULTS: To determine whether the BAFFR antibody prevents atherosclerosis development, we treated ApoE(-/-) mice with the antibody while feeding them a high fat diet (HFD) for 8 weeks. Mature CD93(-) CD19(+) B2 cells were reduced by treatment, spleen B-cell zones disrupted and spleen CD20 mRNA expression decreased while B1a cells and non-B cells were spared. Atherosclerosis was ameliorated in the hyperlipidemic mice and CD19(+) B cells, CD4(+) and CD8(+) T cells were reduced in atherosclerotic lesions. Expressions of proinflammatory cytokines, IL1beta, TNFalpha, and IFNgamma in the lesions were also reduced, while MCP1, MIF and VCAM-1 expressions were unaffected. Plasma immunoglobulins were reduced, but MDA-oxLDL specific antibodies were unaffected. To determine whether anti-BAFFR antibody ameliorates progression of atherosclerosis, we first fed ApoE(-/-) mice a HFD for 6 weeks, and then instigated anti-BAFFR antibody treatment for a further 6 week-HFD. CD93(-) CD19(+) B2 cells were selectively decreased and atherosclerotic lesions were reduced by this treatment. CONCLUSION: Anti-BAFFR monoclonal antibody selectively depletes mature B2 cells while sparing B1a cells, disrupts spleen B-cell zones and ameliorates atherosclerosis development and progression in hyperlipidemic ApoE(-/-) mice. Our findings have potential for clinical translation to manage atherosclerosis-based cardiovascular diseases.
Publisher Public Library of Science
ISSN/ISBN 1932-6203
edoc-URL http://edoc.unibas.ch/dok/A6338183
Full Text on edoc No
Digital Object Identifier DOI 10.1371/journal.pone.0060430
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/23560095
ISI-Number WOS:000318840100070
Document type (ISI) Article
 
   

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28/03/2024