Abstract 570: Deficiency of Inhibitory Fcgamma Receptor II Does Not Exacerbate Atherosclerosis
Objective: Functionally, Fcgamma receptors (FcgRs) can be classified as activating (FcgRI, III, and IV) and inhibitory (FcgRII, CD32b) receptors. We have reported that deletion of activating FcgRs in apoE knockout mice decreased atherosclerosis. In this report we investigated the hypothesis that the deficiency of inhibitory CD32b exacerbates atherosclerosis in a hypercholesterolemic mouse model.
Approach and Results: ApoE-CD32b double knockout mice congenic to the C57BL/6 (apoE-CD32bB6-/-) were generated and atherosclerotic lesions were assessed. Contrary to our hypothesis, arterial lesions were significantly decreased in chow or high fat diet fed apoE-CD32bB6-/- male and female mice, relative to apoE-/- mice. Bone marrow chimera approach using apoE-/- mice transplanted with apoE-CD32bB6-/- marrow also showed significantly reduced arterial lesions. ApoE-CD32bB6-/- mice had increased levels of IL-10 and TGF-b by CD4+ T cells, while IFN-g and IL-17 was decreased. As our findings conflict with a previous report using apoE-CD32b129/6-/- mixed background, we investigated if strain differences contributed to the anti-inflammatory response. Macrophages from mixed apoE-CD32b129/B6-/- mice showed more IL-1b, IL-6 and MCP-1 in response to immune complexes, while congenic CD32bB6-/- mice showed more IL-10 and significantly reduced IL-1b. Interestingly expression of lupus-associated slam genes, located in close proximity to cd32b in mouse chromosome 1, is upregulated only in mixed CD32b129/B6-/- mice.
Conclusions: Our findings demonstrate a detrimental role for CD32b signaling in atherosclerosis and the contribution of anti-inflammatory cytokine responses in the attenuated lesions observed in apoE-CD32bB6-/- mice. As 129/sv genome derived lupus associated genes have been implicated in lupus phenotype in CD32b129/B6-/- mice our findings suggest possible epistatic mechanism contributing to the decreased lesions.
Author Disclosures: S. Nagarajan: None. X. Zhu: None. H. Ng: None.
- © 2015 by American Heart Association, Inc.