Lymphatic blood filling in CLEC-2-deficient mouse models Journal Article
| Authors: | Haining, E. J.; Lowe, K. L.; Wichaiyo, S.; Kataru, R. P.; Nagy, Z.; Kavanagh, D. P.; Lax, S.; Di, Y.; Nieswandt, B.; Ho-Tin-Noé, B.; Mehrara, B. J.; Senis, Y. A.; Rayes, J.; Watson, S. P. |
| Article Title: | Lymphatic blood filling in CLEC-2-deficient mouse models |
| Abstract: | 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. © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. |
| Keywords: | adolescent; adult; controlled study; protein expression; unclassified drug; nonhuman; protein function; animal cell; mouse; animal tissue; animal experiment; carcinogenesis; lymph vessel; podoplanin; blood; platelets; vascular remodeling; lectin receptor; male; female; priority journal; article; blood-lymphatic separation; clec-2; c type lectin like receptor 2 |
| Journal Title: | Platelets |
| Volume: | 32 |
| Issue: | 3 |
| ISSN: | 0953-7104 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2021-01-01 |
| Start Page: | 352 |
| End Page: | 367 |
| Language: | English |
| DOI: | 10.1080/09537104.2020.1734784 |
| PUBMED: | 32129691 |
| PROVIDER: | scopus |
| PMCID: | PMC8443399 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 May 2021 -- Source: Scopus |
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