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  • Deficiency of immunoglobulin E protects mice from experimental abdominal aortic aneurysms.

Deficiency of immunoglobulin E protects mice from experimental abdominal aortic aneurysms.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2020-01-08)
Jie Li, Zhiyong Deng, Xian Zhang, Feng Liu, Chongzhe Yang, Guo-Ping Shi
ABSTRACT

Allergic asthma with high plasma IgE levels is a significant risk factor of human abdominal aortic aneurysm (AAA). This study tests a direct role of IgE in angiotensin-II (Ang-II) perfusion- and peri-aortic CaCl2 injury-induced AAA in mice. In both models, IgE-deficiency in Apoe-/- Ige-/- mice blunts AAA growth and reduces lesion accumulation of macrophages, CD4+ and CD8+ T cells, and lesion MHC class-II expression, CD31+ microvessel growth, and media smooth muscle cell loss, compared with those from Apoe-/- control mice. Real time-PCR reveals significant reductions in expression of neutrophil chemoattractants MIP-2α and CXCL5 in AAA lesions or macrophages from Apoe-/- Ige-/- mice, along with reduced lesion Ly6G+ neutrophil accumulation. Consistent with reduced lesion inflammatory cell accumulation, we find significant reductions of plasma and AAA lesion IL6 expression in Apoe-/- Ige-/- mice. Immunofluorescent staining and FACS analysis show that AAA lesion neutrophils express FcεR1. Mechanistic study demonstrates that IgE induces neutrophil FcεR1 expression, activates MAPK signaling, and promotes IL6 production. This study supports a direct role of IgE in AAA by promoting lesion chemokine expression, inflammatory cell accumulation, MAPK signaling, and cytokine expression. IgE inhibition may represent a novel therapeutic approach in AAA management.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Giemsa Stain, Modified
Sigma-Aldrich
Angiotensin II human, ≥93% (HPLC), powder
Sigma-Aldrich
Anti -Dinitrophenyl antibody, Mouse monoclonal, IgE isotype, ~1 mg/mL, clone SPE-7, affinity purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-Actin, α-Smooth Muscle - FITC antibody, Mouse monoclonal, clone 1A4, purified from hybridoma cell culture
Sigma-Aldrich
Anti-FcεRI Antibody, γ subunit, Upstate®, from rabbit