Abstract 13385: Immunoglobulin E Promotes Vascular Wall Cell Inflammatory Molecule Expression, Apoptosis, and Atherogenesis
Immunoglobulin E (IgE) associates with allergic responses and participates in the activation of mast cells, a cell type implicated in atherogenesis. This study demonstrates elevated serum IgE levels in patients with myocardial infarction or unstable angina pectoris. IgE and its receptor subunit FcεR1α are present in human atherosclerotic lesions, and they localize particularly to areas rich in macrophages. In mice, absence of FcεR1α reduces inflammation and apoptosis in atherosclerotic plaques. In cultured macrophages, the presence of Toll-like receptor 4 (TLR4) is required for FcεR1 activity. IgE stimulates interaction between FcεR1 and TLR4, thereby inducing macrophage signal transduction, inflammatory molecule expression, and apoptosis, which is independent on antigen aggregation. These IgE activities are reduced in the absence of FcεR1 or of TLR4 (but not of TLR2). Furthermore, IgE activates macrophages by enhancing their Na+/H+ exchanger NHE1 activity, thus reducing extracellular pH. Inactivation of NHE1 blocks IgE-induced macrophage inflammatory molecule production and apoptosis. Cultured human aortic smooth-muscle cells (SMCs) and endothelial cells (ECs) also exhibit IgE-induced signal transduction, cytokine expression, and apoptosis, and in human atherosclerotic lesions, SMCs and ECs colocalize with IgE and TUNEL staining. This study reveals several previously unrecognized IgE activities that affect arterial cell biology and likely other IgE-associated pathologies in human diseases.
- © 2011 by American Heart Association, Inc.