Group X secretory PLA2 in neutrophils plays a pathogenic role in abdominal aortic aneurysms in mice
Group X secretory PLA2 in neutrophils plays a pathogenic role in abdominal aortic aneurysms in mice
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中性粒细胞中 X 族分泌型 PLA2 在小鼠腹主动脉瘤中发挥致病作用
DOI：
10.1152/ajpheart.00695.2011
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
et al
中科院分区：
文献类型：
--
作者：
Watanabe K;et al
组X分泌型PLA2（sPLA2-X）在中性粒细胞中表达，并在嗜中性粒细胞介导的组织炎症和损伤的发病机制中起作用。本研究使用sPLA2-X −/−小鼠验证了中性粒细胞中的sPLA2-X可能导致腹主动脉瘤（AAA）发病的假设。腹主动脉瘤通过在主动脉外表面应用CaCl2来创建。结果，与sPLA2-X +/+小鼠相比，sPLA2-X −/−小鼠的动脉直径较小（较基线增加百分比;分别为24.8 ± 3.5%和49.9 ± 9.1%; P <0.01），弹性蛋白降解程度降低，弹性蛋白酶和明胶酶活性较低（分别降低26%和19%）。在sPLA2-X +/+小鼠中，免疫荧光显微图像显示，sPLA2-X仅在CaCl 2处理后3天、1、2和6周的主动脉壁内的中性粒细胞中检测到免疫反应，而在主动脉壁的巨噬细胞和肥大细胞中未检测到免疫反应。sPLA2-X免疫反应性也在表达基质金属蛋白酶（MMP）-9的细胞中共定位。与sPLA2-X +/+小鼠相比，从sPLA2-X −/−小鼠分离的中性粒细胞对刺激的弹性蛋白酶、明胶酶和MMP-9活性较低。sPLA2-X −/−中性粒细胞释放弹性蛋白酶和明胶酶的减弱可通过外源性添加小鼠sPLA2-X蛋白来逆转。CaCl2处理后第0天和第3天过继转移sPLA2-X +/+嗜中性粒细胞，逆转了用sPLA2-X −/−骨髓重建的致死性辐照sPLA2-X +/+小鼠的主动脉直径和弹性蛋白降解等级，其程度与sPLA2-X +/+小鼠相似。总之，中性粒细胞中的sPLA2-X在小鼠模型中的AAA中起致病作用。
Group X secretory PLA2(sPLA2-X) is expressed in neutrophils and plays a role in the pathogenesis of neutrophil-mediated tissue inflammation and injury. This study tested the hypothesis that sPLA2-X in neutrophils may contribute to the pathogenesis of abdominal aortic aneurysms (AAA) using sPLA2-X−/−mice. AAA was created by application of CaCl2to external surface of aorta. As a result, the aortas of sPLA2-X−/−mice had smaller diameters (percent increase from baseline; 24.8 ± 3.5% vs. 49.9 ± 9.1%, respectively;P< 0.01), a reduced grade of elastin degradation, and lower activities of elastase and gelatinase (26% and 19% lower, respectively) after CaCl2treatment compared with sPLA2-X+/+mice. In sPLA2-X+/+mice, immunofluorescence microscopic images showed that the immunoreactivity of sPLA2-X was detected only in neutrophils within aortic walls 3 days, 1, 2, and 6 wk after CaCl2treatment, whereas the immunoreactivity was not detected in macrophages or mast cells in aortic walls. sPLA2-X immunoreactivity also was colocalized in cells expressing matrix metalloproteinase (MMP)-9. Neutrophils isolated from sPLA2-X−/−mice had lower activities of elastase, gelatinase, and MMP-9 in response to stimuli compared with sPLA2-X+/+mice. The attenuated release of elastase and gelatinase from sPLA2-X−/−neutrophils was reversed by exogenous addition of mouse sPLA2-X protein. The adoptive transfer of sPLA2-X+/+neutrophilsdays 0and3after CaCl2treatment reversed aortic diameters and elastin degradation grades in the lethally irradiated sPLA2-X+/+mice reconstituted with sPLA2-X−/−bone marrow to an extent similar to that seen in sPLA2-X+/+mice. In conclusion, sPLA2-X in neutrophils plays a pathogenic role in AAA in a mice model.