(F) Realtime PCR analysis of mouse FcR expression in aortic samples from Sham and Elastase groups (n=8 mice/group). degradation, and VSMC loss. This was associated with (1) reduced infiltrating leukocytes and immune deposits in AAA lesions, (2) inflammatory genes and metalloproteinases downregulation, (3) redox balance restoration, and (4) converse phenotype of antiinflammatory macrophage M2 and contractile VSMC. Adoptive transfer of FcRexpressing macrophages aggravated RG7112 aneurysm in KO mice. In vitro, FcR deficiency attenuated inflammatory gene expression, oxidative stress, and phenotypic switch triggered by IC. Additionally, Syk inhibition prevented ICmediated cell responses, reduced inflammation, and mitigated AAA formation. == Conclusion == Our findings provide insight into the role and mechanisms mediating IgGFcRassociated inflammation and aortic wall injury in AAA, which might represent therapeutic targets against AAA disease. Keywords:abdominal aortic aneurysm, antibodies, autoantigens, Fc receptors, immune system, inflammation, oxidative stress Our work suggests a pathogenic role of IgG IC interaction with activating FcR present in infiltrating and VSMC during AAA formation. These results support the investigation of novel immunotherapeutic strategies targeting FcRs and/or downstream molecules to inhibit humoral immune damage in AAA == Abbreviations == 8hydroxy2deoxyguanosine abdominal aortic aneurysm actin2 Arginase bone marrow CC motif ligand macrophage mannose RG7112 receptor1 CXC motif chemokine 10 dihydroethidium Dulbeccos Modified Eagle Medium foetal bovine serum immunoglobulin G Fc receptor immune complex intercellular adhesion molecule1 interferon immunoglobulin interleukin inducible nitric oxide synthase immunoreceptor tyrosinebased activation motif immunoreceptor tyrosinebased inhibition motif Krueppellike factor4 metalloproteinase nicotine adenine dinucleotide phosphate oxidase smooth muscle protein 22 superoxide dismutase 1 tissue inhibitor of RG7112 metalloproteinase tumour necrosis factor vascular smooth muscle cells Verhoeffvan Gieson wildtype smooth muscle actin chain knockout == 1. INTRODUCTION == Abdominal aortic aneurysm (AAA) is a multifactorial degenerative disease of the aortic wall characterized by progressive weakening and dilation of the abdominal aorta. AAA occurs mainly in adults and causes 1.3% of deaths in men of 6585 years of age in developed countries. Many patients with AAA are asymptomatic and their aneurysmal lesions are detected incidentally on diagnostic imaging. The average growth rate of small AAA is 0.30.5 cm/year; when the aneurysm is symptomatic and/or larger than 5.5 cm in diameter, the surgical repair is indicated to prevent a lifethreatening aortic dissection or rupture.1Besides conventional treatment including lipidlowering drugs, antihypertensives and antiplatelet drugs, new pharmacological therapies to reduce the growth rate of AAA or to prevent its rupture are not sufficiently developed.2This is, in part, because the pathogenic mechanisms contributing to AAA formation and progression are not yet understood. Pathologic features of AAA include progressive destruction of the elastic media layer, vascular smooth muscle cell (VSMC) dysfunction, adventitial and medial inflammatory cell infiltration, and enhanced oxidative stress in the RG7112 vessel wall.3 Nowadays, AAA is considered a chronic inflammatory disease with a strong innate and adaptive immune component.4In AAA lesions, infiltrating immune cells (macrophages, neutrophils, mast cells, B, and T lymphocytes) along with VSMC and fibroblasts, produce cytokines, and matrix metalloproteinases (MMP) that can locally promote an inflammatory reaction, extracellular matrix degradation, VSMC apoptosis, phenotypic switch and neovascularization, further weakening the vessel wall and making it susceptible to rupture.3,5 In contrast to the wellcharacterized function of cellmediated immunity, the role of AXIN2 antibodydependent adaptive immunity in AAA formation is less understood. Studies have detected B cells and their antibodies (predominantly immunoglobulin G [IgG] but also IgM and IgE isotypes) in AAA tissues, mainly distributed in organized folliclelike structures.6,7IgG antibodies from human aneurysmal tissues are immunoreactive with aortic wall components.8,9Circulating and/or tissue levels of IgG against autoantigens (eg, phospholipids, lipoproteins and lipid peroxidation products) are associated with AAA progression.10,11,12In rodents, circulating IgG recognizing specific epitopes in AAA tissues can activate inflammation and complement system,13,14,15,16but the mechanisms and effector molecules remain ambiguous. Aside from their ability to bind to antigens, IgG antibodies and immune complexes (IC) influence inflammation by interacting with receptors specific for the IgG Fc constant region.