Lymphatic blood filling in CLEC-2-deficient mouse models

Elizabeth Haining, Kate Lowe, Surasak Wichaiyo, Raghu P Kataru, Zoltan Nagy, Dean Kavanagh, Sian Lax, Ying Di, Bernhard Nieswandt, Benoît Ho-Tin-Noé, Babak J Mehrara, Yotis Senis, Julie Rayes, Steve Watson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
214 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)352-367
Number of pages16
JournalPlatelets
Volume32
Issue number3
Early online date4 Mar 2020
DOIs
Publication statusPublished - 3 Apr 2021

Bibliographical note

Funding
This work was funded by the Ministry of Sciences and Technology of Thailand and the British Heart Foundation [Grant RG/13/18/30563] and the British Heart Foundation Accelerator Award [AA/18/2/34218]. SPW is a BHF Chair [CH03/003].

Keywords

  • Blood-lymphatic separation
  • CLEC-2
  • platelets
  • podoplanin

ASJC Scopus subject areas

  • Hematology

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