Dystrophin deficiency promotes leukocyte recruitment in mdx mice
Dystrophin deficiency promotes leukocyte recruitment in mdx mice
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DOI：
10.1038/s41390-019-0427-3
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发表时间：
2019-08-01
影响因子：
3.6
通讯作者：
Hudalla, Hannes
中科院分区：
文献类型：
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作者：
Kranig, Simon Alexander;Tschada, Raphaela;Hudalla, Hannes
背景：越来越多的证据将炎症定义为杜氏肌营养不良症发病机制的标志性特征。为了调整潜在的免疫调节干预措施，需要更好地了解杜氏肌营养不良症的免疫失调。我们现在问是否抗肌萎缩蛋白缺乏影响白细胞recreation.METHODS级联：我们进行活体显微镜检查野生型和抗肌萎缩蛋白缺陷mdx小鼠的提睾肌。招募是通过单独准备（创伤性炎症）或与阴囊TNF α注射联合触发的。在组织切片上评估提睾肌的中性粒细胞浸润。通过流式细胞术测定了循环中性粒细胞和促炎细胞因子的血清水平上的整合素表达。结果：Mdx小鼠显示增加滚动和粘附在基线（创伤性炎症）和更深刻的反应后，TNF α注射相比，野生型动物。在这两种模型中，提睾肌的嗜中性细胞浸润增加。上调的整合素LFA-1和Mac-1对循环白细胞和促炎细胞因子IL-6和CCL 2在血清中指向系统性改变的免疫调节mdx mice.CONCLUSION：我们是第一个显示夸大激活的白细胞招募级联在肌营养不良蛋白缺陷的生物体在体内。
BACKGROUND: A growing body of evidence defines inflammation as a hallmark feature of disease pathogenesis of Duchenne muscular dystrophy. To tailor potential immune modulatory interventions, a better understanding of immune dysregulation in Duchenne muscular dystrophy is needed. We now asked whether dystrophin deficiency affects the cascade of leukocyte recruitment.METHODS: We performed intravital microscopy on the cremaster muscle of wild-type and dystrophin-deficient mdx mice. Recruitment was triggered by preparation alone (traumatic inflammation) or in combination with scrotal TNF alpha injections. Neutrophilic infiltration of the cremaster muscle was assessed on tissue sections. Integrin expression on circulating neutrophils and serum levels of pro-inflammatory cytokines were measured by flow cytometry.RESULTS: Mdx mice show increased rolling and adhesion at baseline (traumatic inflammation) and a more profound response upon TNF alpha injection compared with wild-type animals. In both models, neutrophilic infiltration of the cremaster muscle is increased. Upregulation of the integrins LFA-1 and Mac-1 on circulating leukocytes and pro-inflammatory cytokines IL-6 and CCL2 in the serum points toward systemically altered immune regulation in mdx mice.CONCLUSION: We are the first to show exaggerated activation of the leukocyte recruitment cascade in a dystrophin-deficient organism in vivo.