title: IgE stimulates human and mouse arterial cell apoptosis and cytokine expression and promotes atherogenesis in Apoe-/- mice.
abstract: IgE has a key role in the pathogenesis of allergic responses through its ability to activate mast cells via the receptor FcεR1. In addition to mast cells, many cell types implicated in atherogenesis express FcεR1, 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 FcεR1 subunit FcεR1α were present in human atherosclerotic lesions and that they localized particularly to macrophage-rich areas. In mice, absence of FcεR1α reduced inflammation and apoptosis in atherosclerotic plaques and reduced the burden of disease. In cultured macrophages, the presence of TLR4 was required for FcεR1 activity. IgE stimulated the interaction between FcεR1 and TLR4, thereby inducing macrophage signal transduction, inflammatory molecule expression, and apoptosis. These IgE activities were reduced in the absence of FcεR1 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.
authors.affiliation: Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
authors.forename: Mei-Xiang
authors.initials: MX
authors.lastname: Xiang
authors.forename: Mervi
authors.initials: M
authors.lastname: Alanne-Kinnunen
authors.forename: Jian-An
authors.initials: JA
authors.lastname: Wang
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.forename: Aina
authors.initials: A
authors.lastname: He
authors.forename: Xinghui
authors.initials: X
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Tang
authors.forename: Xin
authors.initials: X
authors.lastname: Tu
authors.forename: Sara
authors.initials: S
authors.lastname: Sjöberg
authors.forename: Galina K
authors.initials: GK
authors.lastname: Sukhova
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Liao
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Conrad
authors.forename: Lunyin
authors.initials: L
authors.lastname: Yu
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kawakami
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Shi
mesh_terms: D000787:Angina Pectoris / Q000097:blood / Q000276:immunology / Q000473:pathology; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology*; D002478:Cells, Cultured; D002681:China; D016207:Cytokines / Q000378:metabolism*; D004041:Dietary Fats / Q000009:adverse effects; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000276:immunology / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D004041:Dietary Fats; D017455:Receptors, IgE; D017923:Sodium-Hydrogen Exchangers; D051197:Toll-Like Receptor 4; D007073:Immunoglobulin E