Abstract
Blood platelets have recently been proposed to play a critical role in the development and repair of the lymphatic system. The platelet C-type lectin receptor CLEC-2 and its ligand, the transmembrane protein Podoplanin, which is expressed at high levels on lymphatic endothelial cells (LECs), are required to prevent mixing of the blood and lymphatic vasculatures during mid-gestation. A similar defect is seen in mice deficient in the tyrosine kinase Syk, which plays a vital role in mediating platelet activation by CLEC-2. Furthermore, blood-lymphatic mixing is also present in mice with platelet-/megakaryocyte-specific deletions of CLEC-2 and Syk, suggesting that the phenotype is platelet in origin. The molecular basis of this effect is not known, but it is independent of the major platelet receptors that support hemostasis, including integrin αIIbβ3 (GPIIb-IIIa). Radiation chimeric mice reconstituted with CLEC-2-deficient or Syk-deficient bone marrow exhibit blood-lymphatic mixing in the intestines, illustrating a role for platelets in repair and growth of the lymphatic system. In this review, we describe the events that led to the identification of this novel role of platelets and discuss possible molecular mechanisms and the physiological and pathophysiological significance.
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Acknowledgements
The research in the authors’ laboratory is supported by the Wellcome Trust, British Heart Foundation, and Medical Research Council. We are grateful to Drs Alexander Brill, Craig Hughes, Leyre Navarro-Nunez, and Alice Pollitt for their constructive comments on the manuscript.
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Watson, S.P., Lowe, K., Finney, B.A. (2014). Platelets in Lymph Vessel Development and Integrity. In: Kiefer, F., Schulte-Merker, S. (eds) Developmental Aspects of the Lymphatic Vascular System. Advances in Anatomy, Embryology and Cell Biology, vol 214. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1646-3_8
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DOI: https://doi.org/10.1007/978-3-7091-1646-3_8
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