Fcα Receptor Type I and Its Association with Atherosclerosis Development.

ABSTRACT

Objectives: Atherosclerosis is a chronic inflammatory disease characterized by lipid accumulation and local inflammation, which are regulated by the immune system. The immunological aspects of this disease are unclear. Immunoglobulin A regulates many cell responses through interactions with Fcα receptor type I (FcαRI). Anti-FcαRI antibody inhibits activating receptors by inducing an inhibitory immunoreceptor tyrosine-based activation motif configuration. However, the role of FcαRI in atherosclerosis development is unclear. Here, we investigated the utility of FcαRI targeting to induce inhibitory immunoreceptor tyrosine-based activation motif signaling in atherosclerosis treatment. Materials ApoE-/- transgenic mice expressing the FcαRIR209L/FcRγ chimeric protein (FcαRIR209L/FcRγApoE-/- mice) were generated. We prepared an FcαRIR209L/FcRγ transfectant (I3D) from a mouse macrophage cell line (RAW264.7). Methods: Anti-FcαRI or control antibody was used to investigate a high-fat-diet-induced FcαRIR209L/FcRγApoE-/- mouse model of atherosclerosis. The antibody was also used to assess macrophage foam cell formation via Oil Red O staining and mitogen-activated protein kinase signaling via immunoblotting in the FcαRIR209L/FcRγ-expressing RAW264.7 macrophage cell line I3D. Results: Targeting of monovalent FcαRI induced inhibitory effects in the FcαRIR209L/FcRγApoE-/- mouse model of atherosclerosis by inhibiting macrophage infiltration. FcαRI targeting using the anti-FcαRI antibody also reduced mitogen-activated protein kinase signaling and foam cell formation, leading to decreased interleukin (IL)-1b and monocyte chemoattractant protein (MCP)-1. Conclusions: We demonstrated that targeting monovalent FcαRI suppresses atherosclerosis development. These findings can support the future clinical exploration of FcαRI targeting for atherosclerosis treatment.