Abstract

ABSTRACTMaintenance of blood vessel integrity is crucial for vascular homeostasis and is mainly controlled at the level of endothelial cell (EC) junctions. Regulation of endothelial integrity has largely been investigated in the mature quiescent vasculature. Less is known about how integrity is maintained during vascular growth and remodeling involving extensive junctional reorganization. Here, we show that embryonic mesenteric blood vascular remodeling is associated with a transient loss of venous integrity and concomitant extravasation of red blood cells (RBCs), followed by their clearance by the developing lymphatic vessels. In wild-type mouse embryos, we observed activated platelets extending filopodia at sites of inter-EC gaps. In contrast, embryos lacking the activatory C-type lectin domain family 1, member b (CLEC1B) showed extravascular platelets and an excessive number of RBCs associated with and engulfed by the first lymphatic EC clusters that subsequently form lumenized blood-filled vessels connecting to the lymphatic system. These results uncover novel functions of platelets in maintaining venous integrity and lymphatic vessels in clearing extravascular RBCs during developmental remodeling of the mesenteric vasculature. They further provide insight into how vascular abnormalities characterized by blood-filled lymphatic vessels arise.

Highlights

  • Maintenance of the integrity of blood vessels is crucial for vascular homeostasis, and its disruption can lead to hemorrhage, edema, inflammation and tissue ischemia (Murakami and Simons, 2009)

  • Immunofluorescence combined with differential interference contrast (DIC) imaging of E14 mesenteries from wild-type embryos unexpectedly showed the presence of cells characteristic of red blood cells (RBCs) inside the developing lymphatic vessels (Fig. 1A)

  • Rare extravascular RBCs were observed at E13-E13.5 [0.55±0.57% (n=5) and 2.05±3.07% (n=23) of total RBCs, respectively; Fig. 1D], but the frequency increased to 7.38±7.33% (n=39) at E14 (Fig. 1C,D)

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Summary

Introduction

Maintenance of the integrity of blood vessels is crucial for vascular homeostasis, and its disruption can lead to hemorrhage, edema, inflammation and tissue ischemia (Murakami and Simons, 2009). We further identify previously unrecognized roles of platelets and lymphatic vessels during developmental vessel remodeling in maintaining endothelial integrity and clearing of red blood cells (RBCs), respectively.

Results
Conclusion

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