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Characterization of a novel mouse model with genetic deletion of CD177
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  • 分类:Q78[生物学—分子生物学] TS218[轻工技术与工程—粮食、油脂及植物蛋白工程;轻工技术与工程—食品科学与工程]
  • 作者机构:[1]College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China, [2]Department of Pathology, Holden Comprehensive Cancer Center, Carver College of Medicine/University of Iowa, Iowa, IA 52242, USA, [3]Department of Internal Medicine, Carver College of Medicine/University of Iowa, Iowa, IA 52242, USA, [4]Department of Pharmacology, Carver College of Medicine/University of Iowa, Iowa, IA 52242, USA, [5]National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China, [6]Beijing Institute for Brain Disorders, Beijing 100069, China
  • 相关基金:We sincerely thank Drs. Tang and Coldren for sharing the microarray datasets. The CD177 mouse strain used for this research project was created from an ES cell clone (12120a-B11) obtained from the KOMP Repository (www.komp.org) and generated by Regeneron Pharmaceuticals, Inc. This work was supported by NIH grant CA158055 (W.Z.) and NIH T32 GM007337 (N.B.). Additionally, W.Z. was supported by depart- mental start up funds, and seed grants from the Department of Pathology at the University of Iowa Carver College of Medicine and from the American Cancer Society. G.H.L. was supported by the National Basic Research Program (973 Program) (Nos. 2015CB964800 and 2014CB964600), the Strategic Priority Research Program of the Chi- nese Academy of Sciences (XDA01020312), the National Natural Science Foundation of China (Grant Nos. 81271266, 31222039, 81330008, 31201111, and 81300677), Beijing Natural Science Foun- dation (7141005), and the Thousand Young Talents program of China, and State Key Laboratory of Drug Research (SIMM1302KF-17). Q.X. was supported by a scholarship from the China Scholarship Council.
中文摘要:

Neutrophils 玩在对感染的天生的有免疫力的反应的一个必要角色。Neutrophils 响应感染从 vasculature 移居进织物。最近,嗜中性的房间表面受体, CD177,被显示帮助调停越过通过和 PECAM1 的相互作用的内皮细胞层的嗜中性的移植。我们从跟随肺的内毒素灌输的人的 neutrophils 检验了 CD177 表示的公开可得到的基因数组数据集。在检验的所有 22,214 基因之中, CD177 mRNA 是大多数 upregulated 追随者内毒素暴露。CD177 表示的高水平也在上空 neutrophils 被维持,建议在在传染疾病下面的嗜中性的渗入的 CD177 的潜在的参与。在 vivo 在 neutrophils 决定 CD177 的角色,我们构造了一个 CD177 基因的猛烈老鼠模型。有 CD177 的同型结合的删除的老鼠没在有免疫力的房间有看得清的显型和没有重要变化,除在外部血的减少的嗜中性的计数以外。我们与葡萄球菌 aureus 用一个皮肤感染模型在嗜中性的累积检验了 CD177 的角色。CD177 删除在 S 引起的煽动性的皮肤减少了嗜中性的计数。aureus。机械学地,我们发现在老鼠 neutrophils 的那 CD177 删除没在导致 CXCL1/KC 或导致 fMLP 的移植有重要影响,但是导致了重要房间死亡。此处,我们建立了一个新奇基因老鼠模型学习 CD177 的角色并且发现 CD177 在 neutrophils 起一个重要作用。

英文摘要:

Neutrophils play an essential role in the innate immune response to infection. Neutrophils migrate from the vasculature into the tissue in response to infection. Recently, a neutrophil cell surface receptor, CD177, was shown to help mediate neutrophil migration across the endothelium through interactions with PECAMI. We examined a publicly available gene array dataset of CD177 expression from human neutrophils following pulmonary endotoxin instillation. Among all 22,214 genes examined, CD177 mRNA was the most upregu- lated following endotoxin exposure. The high level of CD177 expression is also maintained in airspace neu- trophils, suggesting a potential involvement of CD177 in neutrophil infiltration under infectious diseases. To determine the role of CD177 in neutrophils in vivo, we constructed a CD177-genetic knockout mouse model. The mice with homozygous deletion of CD177 have no discernible phenotype and no significant change in immune cells, other than decreased neutrophil counts in peripheral blood. We examined the role of CD177 in neutrophil accumulation using a skin infection model with Staphylococcus aureus. CD177 deletion reducedneutrophil counts in inflammatory skin caused by S. aureus. Mechanistically we found that CD177 deletion in mouse neutrophils has no significant impact in CXCLI/ KC- or fMLP-induced migration, but led to significant cell death. Herein we established a novel genetic mouse model to study the role of CD177 and found that CD177 plays an important role in neutrophils.

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