Eosinophils Protect Mice From Angiotensin-II Perfusion-Induced Abdominal Aortic Aneurysm.
Eosinophils Protect Mice From Angiotensin-II Perfusion-Induced Abdominal Aortic Aneurysm.
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嗜酸性粒细胞保护小鼠免受血管紧张素 II 灌注诱发的腹主动脉瘤。
DOI：
10.1161/circresaha.120.318182
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发表时间：
2021-01-22
影响因子：
20.1
通讯作者：
Shi GP
中科院分区：
文献类型：
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作者：
Liu CL;Liu X;Zhang Y;Liu J;Yang C;Luo S;Liu T;Wang Y;Lindholt JS;Diederichsen A;Rasmussen LM;Dahl M;Sukhova GK;Lu G;Upchurch GR;Libby P;Guo J;Zhang J;Shi GP
血液嗜酸性粒细胞（EOS）计数和EOS阳离子蛋白（ECP）与人类心血管疾病（CVD）相关。然而，EOS是否在CVD中发挥作用仍未得到验证。目前的研究发现EOS在人和鼠腹主动脉瘤（AAA）病变中积累，提示EOS参与了这种主动脉疾病。测试EOS是否以及如何影响AAA的增长。基于人群的随机临床对照筛查试验显示，579名男性AAA患者的血液EOS计数高于5063名非AAA对照组（0.236±0.182 vs 0.211±0.154,109/L， P<0.001）。单因素logistic回归分析（OR=1.381， P<0.001）和多因素logistic回归分析（OR=1.237， P=0.031）表明，AAA患者血液中EOS计数升高是人AAA的独立危险因素。免疫染色和免疫印迹分析检测了人和鼠AAA病变中EOS的积累和EOS正离子蛋白的表达。结果表明，在Apoe - / -和EOS缺乏的Apoe - / -ΔdblGATA小鼠中，血管紧张素- ii灌注诱导AAA时，EOS缺乏加剧了AAA的生长，增加了病变炎症细胞含量、基质降解蛋白酶活性、血管生成、细胞增殖和凋亡以及平滑肌细胞（SMC）损失。EOS缺乏增加病变趋化因子表达，减弱病变il - 4和EOS相关核酶-1 （mEar1，人ECP同源物）的表达，以及M1巨噬细胞偏斜极化。在培养的巨噬细胞和单核细胞中，eos来源的IL4和mEar1使M2巨噬细胞极化，抑制CD11b+Ly6Chi单核细胞，增加CD11b+Ly6Clo单核细胞。mEar1处理或从WT和Il13 - / -小鼠中过继转移EOS，而不是从Il4 - / -小鼠中过继转移EOS，可阻断Apoe - / -ΔdblGATA小鼠的AAA生长。免疫荧光染色和免疫印迹分析显示，EOS il - 4和mEar1可阻断巨噬细胞、SMCs和内皮细胞中NF-κB的激活。EOS通过释放IL4和mEar1等阳离子蛋白，调节巨噬细胞和单核细胞极化，阻断主动脉炎症和血管细胞NF-κB活化，在AAA中发挥保护作用。
Blood eosinophil (EOS) count and EOS cationic protein (ECP) associate with human cardiovascular diseases (CVD). Yet, whether EOS play a role in CVD remains untested. The current study detected EOS accumulation in human and murine abdominal aortic aneurysm (AAA) lesions, suggesting EOS participation in this aortic disease. To test whether and how EOS affect AAA growth. Population-based randomized clinically controlled screening trials revealed higher blood EOS count in 579 male AAA patients than in 5,063 non-AAA control (0.236±0.182 vs 0.211±0.154, 109/L, P<0.001). Univariate (OR=1.381, P<0.001) and multivariate (OR=1.237, P=0.031) logistic regression analyses indicated that increased blood EOS count in AAA patients served as an independent risk factor of human AAA. Immunostaining and immunoblot analyses detected EOS accumulation and EOS cationic protein expression in human and murine AAA lesions. Results showed that EOS deficiency exacerbated AAA growth with increased lesion inflammatory cell contents, matrix-degrading protease activity, angiogenesis, cell proliferation and apoptosis, and smooth muscle cell (SMC) loss using angiotensin-II perfusion-induced AAA in Apoe–/– and EOS-deficient Apoe–/–ΔdblGATA mice. EOS deficiency increased lesion chemokine expression, muted lesion expression of IL4 and EOS-associated-ribonuclease-1 (mEar1, human ECP homolog), and slanted M1 macrophage polarization. In cultured macrophages and monocytes, EOS-derived IL4 and mEar1 polarized M2 macrophages, suppressed CD11b+Ly6Chi monocytes, and increased CD11b+Ly6Clo monocytes. mEar1 treatment or adoptive transfer of EOS from WT and Il13–/– mice, but not EOS from Il4–/– mice, blocked AAA growth in Apoe–/–ΔdblGATA mice. Immunofluorescent staining and immunoblot analyses demonstrated a role for EOS IL4 and mEar1 in blocking NF-κB activation in macrophages, SMCs, and endothelial cells. EOS play a protective role in AAA by releasing IL4 and cationic proteins such as mEar1 to regulate macrophage and monocyte polarization and to block NF-κB activation in aortic inflammatory and vascular cells.
DOI：
10.4049/jimmunol.1003353
发表时间：
2011-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Sofi MH;Qiao Y;Ansel KM;Kubo M;Chang CH
通讯作者：
Chang CH