1. IgE stimulates human and mouse arterial cell apoptosis and cytokine expression and promotes atherogenesis in [Apoe.sup.-/-] mice
- Author
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Wang, Jing, Cheng, Xiang, Xiang, Mei-Xiang, Alanne-Kinnunen, Mervi, Wang, Jian-An, Chen, Han, He, Aina, Sun, Xinghui, Lin, Yan, Tang, Ting-Ting, Tu, Xin, Sjoberg, Sara, Sukhova, Galina K., Liao, Yu-Hua, Conrad, Daniel H., Yu, Lunyin, Kawakami, Toshiaki, Kovanen, Petri T., Libby, Peter, and Shi, Guo-Ping
- Subjects
Cytokines -- Properties ,Macrophages -- Growth -- Genetic aspects ,Apoptosis -- Genetic aspects ,Immunoglobulin E -- Properties ,Company growth ,Health care industry - Abstract
IgE has a key role in the pathogenesis of allergic responses through its ability to activate mast cells via the receptor FcζR1. In addition to mast cells, many cell types implicated in atherogenesis express FcζR1, but whether IgE has a role in this disease has not been determined. Here, we demonstrate that serum IgE levels are elevated in patients with myocardial infarction or unstable angina pectoris. We found that IgE and the FcζR1 subunit FcζR1 α were present in human atherosclerotic lesions and that they localized particularly to macrophage-rich areas. In mice, absence of FcζR1α reduced inflammation and apoptosis in atherosclerotic plaques and reduced the burden of disease. In cultured macrophages, the presence of TLR4 was required for FcζR1 activity. IgE stimulated the interaction between FcζR1 and TLR4, thereby inducing macrophage signal transduction, inflammatory molecule expression, and apoptosis. These IgE activities were reduced in the absence of FcζR1 or TLR4. Furthermore, IgE activated macrophages by enhancing [[Na.sup.+]/H.sup.+] exchanger 1 (NHE1) activity. Inactivation of NHE1 blocked IgE-induced macrophage production of inflammatory molecules and apoptosis. Cultured human aortic SMCs (HuSMCs) and ECs also exhibited IgE-induced signal transduction, cytokine expression, and apoptosis. In human atherosclerotic lesions, SMCs and ECs colocalized with IgE and TUNEL staining. This study reveals what we believe to be several previously unrecognized IgE activities that affect arterial cell biology and likely other IgE-associated pathologies in human diseases., Introduction IgE is an important regulator of allergic reactions, in which it activates mast cells (MCs) by binding to its high-affinity receptor FcζR1 (1). In addition to allergic responses (2), [...]
- Published
- 2011
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