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Review
. 2022 Aug 15;12(8):a041274.
doi: 10.1101/cshperspect.a041274.

Lymphatic Vascular Permeability

Joshua P Scallan  1 , Melanie Jannaway  1
Affiliations
Review

Lymphatic Vascular Permeability

Joshua P Scallan et al. Cold Spring Harb Perspect Med. .

Abstract

Blood vessels have a regulated permeability to fluid and solutes, which allows for the delivery of nutrients and signaling molecules to all cells in the body, a process essential to life. The lymphatic vasculature is the second network of vessels in the body, making up part of the immune system, yet is not typically thought of as having a permeability to fluid and solute. However, the major function of the lymphatic vasculature is to regulate tissue fluid balance to prevent edema, so lymphatic vessels must be permeable to absorb and transport fluid efficiently. Only recently were lymphatic vessels discovered to be permeable, which has had many functional implications. In this review, we will provide an overview of what is known about lymphatic vascular permeability, discuss the biophysical and signaling mechanisms regulating lymphatic permeability, and examine the disease relevance of this new property of lymphatic vessels.

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Figures

Figure 1.
Figure 1.
Working hypothesis of button junction formation in the intestinal lacteals. After birth, the lymphatic lacteals remodel their zipper junctions to form button junctions (see inset, top left). The constant expression of Nrp1/Flt1 receptors act as scavengers for VEGF-A, which maintains button morphology. In the absence of these receptors, excess VEGF-A enhances VEGFR2 activation and signaling, leading to zippering of the lacteal junctions (inset, top right). Increased inflammation from infectious pathogens can also cause zippering of the lacteals, which can be reversed by treatment with dexamethasone. Genetic deletion of DLL4 or angiopoietin 2 (ANGPT2), or inhibition of ROCK all cause zippering of the lacteal junctions. Loss of CD36 appears to loosen the button junctions further and may affect VE-cadherin expression in the lacteals, which is associated with weight gain and obesity (inset, bottom). Figure was created with BioRender (BioRender.com).
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