Lymphatic blood filling in CLEC-2-deficient mouse models

Haining Elizabeth J.; Lowe Kate L.; Wichaiyo Surasak; Kataru Raghu P.; Nagy Zoltan; Kavanagh Dean Pj; Lax Sian; Di Ying; Nieswandt Bernhard; Ho-Tin-Noe Benoit; Mehrara Babak J.; Senis Yotis A.; Rayes Julie; Watson Steve P.

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Lymphatic blood filling in CLEC-2-deficient mouse models

机译：淋巴血液填充CLEC-2缺乏小鼠模型

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C-type lectin-like receptor 2 (CLEC-2) is considered as a potential drug target in settings of wound healing, inflammation, and infection. A potential barrier to this is evidence that CLEC-2 and its ligand podoplanin play a critical role in preventing lymphatic vessel blood filling in mice throughout life. In this study, this aspect of CLEC-2/podoplanin function is investigated in more detail using new and established mouse models of CLEC-2 and podoplanin deficiency, and models of acute and chronic vascular remodeling. We report that CLEC-2 expression on platelets is not required to maintain a barrier between the blood and lymphatic systems in unchallenged mice, post-development. However, under certain conditions of chronic vascular remodeling, such as during tumorigenesis, deficiency in CLEC-2 can lead to lymphatic vessel blood filling. These data provide a new understanding of the function of CLEC-2 in adult mice and confirm the essential nature of CLEC-2-driven platelet activation in vascular developmental programs. This work expands our understanding of how lymphatic blood filling is prevented by CLEC-2-dependent platelet function and provides a context for the development of safe targeting strategies for CLEC-2 and podoplanin.

机译：C型凝集素样受体2（CLEC-2）被认为是伤口愈合、炎症和感染的潜在药物靶点。一个潜在的障碍是，有证据表明CLEC-2及其配体波多普兰在预防小鼠一生中淋巴管血管充盈方面起着关键作用。在本研究中，使用新建立的小鼠CLEC-2和Podoplan缺乏模型，以及急性和慢性血管重塑模型，对CLEC-2/Podoplan功能的这一方面进行了更详细的研究。我们报告，在发育后未受挑战的小鼠中，血小板上的CLEC-2表达不需要维持血液和淋巴系统之间的屏障。然而，在某些慢性血管重塑条件下，例如在肿瘤发生过程中，CLEC-2缺乏可导致淋巴管血管充盈。这些数据提供了对成年小鼠CLEC-2功能的新理解，并证实了血管发育程序中CLEC-2驱动的血小板活化的本质。这项工作扩展了我们对CLEC-2依赖性血小板功能如何阻止淋巴管血液充盈的理解，并为CLEC-2和波多普兰的安全靶向策略的开发提供了背景。

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《Platelets》 |2021年第3期|共16页
作者
Haining Elizabeth J.; Lowe Kate L.; Wichaiyo Surasak; Kataru Raghu P.; Nagy Zoltan; Kavanagh Dean Pj; Lax Sian; Di Ying; Nieswandt Bernhard; Ho-Tin-Noe Benoit; Mehrara Babak J.; Senis Yotis A.; Rayes Julie; Watson Steve P.;
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作者单位

Univ Birmingham Inst Cardiovasc Sci Coll Med &

Dent Sci Birmingham B15 2TT W Midlands England;

Univ Birmingham Inst Cardiovasc Sci Coll Med &

Dent Sci Birmingham B15 2TT W Midlands England;

Univ Birmingham Inst Cardiovasc Sci Coll Med &

Dent Sci Birmingham B15 2TT W Midlands England;

Mem Sloan Kettering Canc Ctr Dept Surg Div Plast &

Reconstruct Surg 1275 York Ave New York NY;

Univ Birmingham Inst Cardiovasc Sci Coll Med &

Dent Sci Birmingham B15 2TT W Midlands England;

Univ Birmingham Inst Cardiovasc Sci Coll Med &

Dent Sci Birmingham B15 2TT W Midlands England;

Univ Birmingham Inst Cardiovasc Sci Coll Med &

Dent Sci Birmingham B15 2TT W Midlands England;

Univ Birmingham Inst Cardiovasc Sci Coll Med &

Dent Sci Birmingham B15 2TT W Midlands England;

Univ Wurzburg Rudolf Virchow Ctr Expt Biomed Wurzburg Germany;

Univ Paris Diderot Hop Bichat Sorbonne Paris Cite INSERM UMR S1148 Paris France;

Mem Sloan Kettering Canc Ctr Dept Surg Div Plast &

Reconstruct Surg 1275 York Ave New York NY;

Univ Birmingham Inst Cardiovasc Sci Coll Med &

Dent Sci Birmingham B15 2TT W Midlands England;

Univ Birmingham Inst Cardiovasc Sci Coll Med &

Dent Sci Birmingham B15 2TT W Midlands England;

Univ Birmingham Inst Cardiovasc Sci Coll Med &

Dent Sci Birmingham B15 2TT W Midlands England;

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原文格式 PDF
正文语种 eng
中图分类基础医学;
关键词
Blood-lymphatic separation; CLEC-2; platelets; podoplanin;

机译：血液淋巴分离;CLEC-2;血小板;泛骨膜蛋白;

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2. Anti—inflammatory effect of cerivastatin in vascular injury independent of serum cholesterol and blood pressure lowering effects in mouse model [J] . 陈小东, 李震, 等中华创伤杂志：英文版 . 2002,第005期
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4. Postnatal Deletion of Podoplanin in Lymphatic Endothelium Results in Blood Filling of the Lymphatic System and Impairs Dendritic Cell Migration to Lymph Nodes [J] . Bianchi Roberta, Russo Erica, Bachmann Samia B., Arteriosclerosis, thrombosis, and vascular biology . 2017,第1期

机译：淋巴内皮中泛吡铂的后期缺失导致淋巴系统的血液填充，损害树突细胞迁移到淋巴结
5. Postnatal Deletion of Podoplanin in Lymphatic Endothelium Results in Blood Filling of the Lymphatic System and Impairs Dendritic Cell Migration to Lymph Nodes [J] . Bianchi Roberta, Russo Erica, Bachmann Samia B., Arteriosclerosis, thrombosis, and vascular biology . 2017,第1期

机译：淋巴内皮中泛吡铂的后期缺失导致淋巴系统的血液填充，损害树突细胞迁移到淋巴结
6. Visualization of fluid drainage pathways in lymphatic vessels and lymph nodes using a mouse model to test a lymphatic drug delivery system [J] . Tetsuya Kodama Yuriko Hatakeyama Shigeki Kato, Shiro Mori Biomedical Optics Express . 2015,第1期

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8. The adhesive interactions between metastatic melanoma cells and lymphatic endothelial cells in a mouse model. [D] . Lizardo, Michael M. 2005

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10. Lymphatic blood filling in CLEC-2-deficient mouse models [O] . Elizabeth J Haining, Kate L Lowe, Surasak Wichaiyo, 2020

机译：淋巴血液填充CLEC-2缺乏小鼠模型
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机译：核心模块化血液和脑生物标志物在社会失败小鼠模型创伤后应激障碍。

Lymphatic blood filling in CLEC-2-deficient mouse models

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