Lymphatic blood filling in CLEC-2-deficient mouse models
| Title: | Lymphatic blood filling in CLEC-2-deficient mouse models |
|---|---|
| Authors: | Elizabeth J Haining, Kate L Lowe, Surasak Wichaiyo, Raghu P Kataru, Zoltan Nagy, Dean Pj Kavanagh, Sian Lax, Ying Di, Bernhard Nieswandt, Benoît Ho-Tin-Noé, Babak J Mehrara, Yotis A Senis, Julie Rayes, Steve P Watson |
| Source: | Platelets, Vol 32, Iss 3, Pp 352-367 (2021) |
| Publisher Information: | Taylor & Francis Group, 2021. |
| Publication Year: | 2021 |
| Collection: | LCC:Diseases of the blood and blood-forming organs |
| Subject Terms: | blood-lymphatic separation, clec-2, platelets, podoplanin, Diseases of the blood and blood-forming organs, RC633-647.5 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 0953-7104 1369-1635 09537104 |
| Relation: | https://doaj.org/toc/0953-7104; https://doaj.org/toc/1369-1635 |
| DOI: | 10.1080/09537104.2020.1734784 |
| Access URL: | https://doaj.org/article/a005fc05380f45788ba6052de9029753 |
| Accession Number: | edsdoj.005fc05380f45788ba6052de9029753 |
| Database: | Directory of Open Access Journals |
| ISSN: | 09537104 13691635 |
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| DOI: | 10.1080/09537104.2020.1734784 |
| Published in: | Platelets |
| Language: | English |