Current views on the function of the lymphatic vasculature in health and disease

Wang, Yingdi; Oliver, Guillermo

doi:10.1101/gad.1955910

Cited by 158 publications

(143 citation statements)

References 142 publications

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“…The mammalian lymphatic system consists of blind-ending lymphatic vessels, lymph nodes and other tissues, including the spleen, that collect, filter and return fluid that drains from the tissues to the venous system and transport fats and proteins from the gut into the blood system (Alitalo et al, 2005;Wang and Oliver, 2010). In teleost fishes, some circulatory vessels contain clear fluid and have been described as lymphatic vessels (Kampmeier, 1969).…”

Section: Introductionmentioning

confidence: 99%

Function and control of the fish secondary vascular system, a contrast to mammalian lymphatic systems

Rummer

Wang

Steffensen

et al. 2013

Journal of Experimental Biology

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Teleost fishes and mammalian lineages diverged 400 million years ago, and environmental requirements (water versus air) have resulted in marked differences in cardiovascular function between fish and mammals. Suggestions that the fish secondary vascular system (SVS) could be used as a model for the mammalian lymphatic system should be taken with caution. Despite molecular markers indicating similar genetic origin, functions of the SVS in teleost fish are probably different from those of the mammalian lymphatic system. We determined that, in resting glass catfish (Kryptopterus bicirrhis), plasma moves from the primary vascular system (PVS) to the SVS through small connecting vessels less than 10 μm in diameter, smaller than the red blood cells (RBCs). During and following hypoxia or exercise, flow increases and RBCs enter the SVS, possibly via β-adrenoreceptor-mediated dilation of the connecting vessels. The volume of the SVS can be large and, as RBCs flow into the SVS, the haematocrit of the PVS falls by as much as 50% of the resting value. Possible functions of the SVS, including skin respiration, ionic and osmotic buffering, and reductions in heart work and RBC turnover, are discussed. KEY WORDS: Lymphatic, Secondary vascular system, Stress INTRODUCTIONThe mammalian lymphatic system consists of blind-ending lymphatic vessels, lymph nodes and other tissues, including the spleen, that collect, filter and return fluid that drains from the tissues to the venous system and transport fats and proteins from the gut into the blood system (Alitalo et al., 2005;Wang and Oliver, 2010). In teleost fishes, some circulatory vessels contain clear fluid and have been described as lymphatic vessels (Kampmeier, 1969). Yaniv et al. (Yaniv et al., 2006) and Isogai et al. (Isogai et al., 2009) have also demonstrated that these vessels share some morphological and molecular characteristics with the lymphatic vessels found in other vertebrates, and suggested that these clear vessels in zebrafish could be used as a model for the mammalian lymphatic system. However, several decades ago these same vessels were hypothesized as part of a secondary vascular system (SVS), receiving inflow from the arterial system via arterio-arterial anastomoses and emptying into the venous circulation (Vogel, 1981;Vogel and Claviez, 1981;Vogel, 1985;Steffensen et al., 1986;Steffensen and Lomholt, 1992; RESEARCH ARTICLE Jensen et al., 2009). These vessels are not blind-ending and sometimes include red blood cells (RBCs) (Ishimatsu et al., 1992). Furthermore, there is no evidence that the SVS vessels are draining edematous tissues or are playing a role in lipid transport. If not lymphatic, what then is the role of this secondary vascular system?The volume of the SVS can range from 10-50% to nearly twice the volume of the primary circulation (Bushnell et al., 1998;Gallaugher and Farrell, 1998;Skov and Steffensen, 2003;Steffensen and Lomholt, 1992) and therefore may serve to buffer osmotic and ionic changes in the primary circulation. Under restin...

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Section: Introductionmentioning

confidence: 99%

Function and control of the fish secondary vascular system, a contrast to mammalian lymphatic systems

Rummer

Wang

Steffensen

et al. 2013

Journal of Experimental Biology

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“…Although blood vessel and lymphatic endothelium share many characteristics including expression of certain same molecules, they also have striking differences regarding their morphology, function, and molecular profile. [1][2][3] Balance of extracellular ATP metabolism on endothelium controls the inflammatory status of the microenvironment as ATP is highly proinflammatory and ADP procoagulative while adenosine is anti-inflammatory. 4 CD73 is a key enzyme in extracellular ATP metabolism producing adenosine by dephosphorylating AMP.…”

Section: Introductionmentioning

confidence: 99%

Different role of CD73 in leukocyte trafficking via blood and lymph vessels

Ålgars

Karikoski

Yegutkin

et al. 2011

Blood

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CD73 is involved in the extracellular ATP metabolism by dephosphorylating extracellular AMP to adenosine and thus regulating permeability of the blood vessels and leukocyte traffic into the tissues. It is also present on lymphatic vessels where its distribution and function have not been characterized. We found that CD73 is expressed on a subpopulation of afferent lymph vessels but is absent on efferent lymphatics, unlike LYVE-1 and podoplanin, which are expressed on both types of lymphatics. The extracellular nucleotide metabolism on lymphatic endothelium differs from that on blood vessel endothelium as lymphatic endothelium has lower NTPDase and higher ecto-5-nucleotidase/CD73 activity than blood vascular endothelium. In knockout mice, the lack of CD73 on lymphocytes decreases migration of lymphocytes to the draining lymph nodes more than 50% while CD73-deficient lymph vessels mediate lymphocyte trafficking as efficiently as the wild-type lymphatics. Thus, although endothelial CD73 is important for permeability and leukocyte extravasation in blood vessels, it does not have a role in these functions on lymphatics. Instead, lymphocyte CD73 is intimately involved in lymphocyte migration via afferent lymphatic vessels. (Blood. 2011;117(16): 4387-4393) IntroductionContinuous recirculation of lymphocytes between blood and lymphoid tissues is central for proper functioning of the immune system, and leukocyte entrance to the sites of infections is required for elimination of intruding pathogens. Proper interaction between leukocytes and endothelial cells both in blood and lymphatic vessels is central for leukocyte trafficking. Although blood vessel and lymphatic endothelium share many characteristics including expression of certain same molecules, they also have striking differences regarding their morphology, function, and molecular profile. [1][2][3] Balance of extracellular ATP metabolism on endothelium controls the inflammatory status of the microenvironment as ATP is highly proinflammatory and ADP procoagulative while adenosine is anti-inflammatory. 4 CD73 is a key enzyme in extracellular ATP metabolism producing adenosine by dephosphorylating AMP. [5][6][7] Besides on blood vessels, 8 CD73 is also expressed on a subpopulation of lymphocytes. 9 Regulatory T cells are especially CD73 positive. 10 Although CD73 on the endothelial cells and lymphocytes are structurally similar, they are differently regulated. Triggering of lymphocyte CD73 with antibodies results in cleavage of CD73 and activation of LFA-1 leading to increased adhesion of lymphocytes to endothelium. Engagement of endothelial CD73, in contrast, does not cause cleavage of the molecule from the cell surface. 11 The central role of CD73 in vascular permeability is well demonstrated in mice deficient with CD73. They show normal lymphocyte homing in nonchallenged conditions, but in hypoxic and inflammatory conditions increased endothelial leakiness and leukocyte extravasation via high endothelial venules (HEV) are observed 12 with a concordant exacerbation...

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“…The lymphatic vascular system is considered as the body's second circulation system and is essential for maintaining interstitial fluid pressure equilibrium and transporting tissue fluid, proteins, and cells (Wang & Oliver 2010). The lymphatic system is also crucial during the immune response to infectious agents, as lymphatic vessels are the route by which dendritic cells and macrophages migrate to the lymph nodes and lymphoid organs to present antigen to T cells.…”

Section: Introductionmentioning

confidence: 99%

Possible involvement of IFNT in lymphangiogenesis in the corpus luteum during the maternal recognition period in the cow

Nitta¹,

Shirasuna²,

Haneda³

et al. 2011

Reproduction

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The corpus luteum (CL), which secretes large amounts of progesterone and is thus essential for establishing pregnancy, contains various types of immune cells that may play essential roles in CL function by generating immune responses. The lymphatic system is the second circulation system and is necessary for immune function, but the lymphatic system of the bovine CL has not been characterized in detail. We collected bovine CLs on days 12 and 16 of the estrous cycle (C12 and C16) and days 16 and 40 of early pregnancy (P16 and P40). Lymphatic endothelial hyaluronan receptor 1 (LYVE1) protein was detected in the CL by immunohistochemistry and western blotting and increased at P40 compared with C16. The mRNA expression levels of lymphangiogenic factors, such as vascular endothelial growth factor-C (VEGFC), VEGFD, and their common receptor VEGFR3, as well as the lymphatic endothelial cell (LyEC) marker podoplanin, increased in P16 and P40 CLs. Thus, it is suggested that the lymphatic system of the bovine CL reconstitutes during early pregnancy. Interferon tau (IFNT) from the conceptus in the uterus is a candidate for activating luteal lymphangiogenesis during the maternal recognition period (MRP). We found that treatment of LyECs isolated from internal iliac lymphatic vessels with IFNT stimulated LyEC proliferation and significantly increased mRNA expression of VEGFC and IFN-stimulated gene 15. Moreover, both IFNT and VEGFC induced LyECs to form capillary-like tubes in vitro.In conclusion, it is suggested that new lymphangiogenesis in the bovine CL begins during the MRP and that IFNT may mediate this novel phenomenon.

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Current views on the function of the lymphatic vasculature in health and disease

Cited by 158 publications

References 142 publications

Function and control of the fish secondary vascular system, a contrast to mammalian lymphatic systems

Function and control of the fish secondary vascular system, a contrast to mammalian lymphatic systems

Different role of CD73 in leukocyte trafficking via blood and lymph vessels

Possible involvement of IFNT in lymphangiogenesis in the corpus luteum during the maternal recognition period in the cow

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