| First Author | Wang J | Year | 2011 |
| Journal | J Clin Invest | Volume | 121 |
| Issue | 9 | Pages | 3564-77 |
| PubMed ID | 21821913 | Mgi Jnum | J:178258 |
| Mgi Id | MGI:5297767 | Doi | 10.1172/JCI46028 |
| Citation | Wang J, et al. (2011) IgE stimulates human and mouse arterial cell apoptosis and cytokine expression and promotes atherogenesis in Apoe-/- mice. J Clin Invest 121(9):3564-77 |
| abstractText | IgE has a key role in the pathogenesis of allergic responses through its ability to activate mast cells via the receptor FcepsilonR1. In addition to mast cells, many cell types implicated in atherogenesis express FcepsilonR1, 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 FcepsilonR1 subunit FcepsilonR1alpha were present in human atherosclerotic lesions and that they localized particularly to macrophage-rich areas. In mice, absence of FcepsilonR1alpha reduced inflammation and apoptosis in atherosclerotic plaques and reduced the burden of disease. In cultured macrophages, the presence of TLR4 was required for FcepsilonR1 activity. IgE stimulated the interaction between FcepsilonR1 and TLR4, thereby inducing macrophage signal transduction, inflammatory molecule expression, and apoptosis. These IgE activities were reduced in the absence of FcepsilonR1 or TLR4. Furthermore, IgE activated macrophages by enhancing Na+/H+ 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. |
