Mechanosensation and Mechanotransduction by Lymphatic Endothelial Cells Act as Important Regulators of Lymphatic Development and Function

Bálint, László; Jakus, Zoltán

doi:10.3390/ijms22083955

Cited by 14 publications

(6 citation statements)

References 226 publications

(212 reference statements)

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“…Emerging evidence suggests that neutrophils may also interact with the lymphatic system by regulating lymphangiogenesis (or growth of new lymphatic vessels) in inflamed tissues and lymph nodes during inflammation and cancer progression [3,95]. Recent studies have identified signals which promote the formation of the lymphatic vasculature [96,97]. Vascular endothelial growth factors, such as VEGF-A, VEGF-C and VEGF-D can induce LEC sprouting and proliferation.…”

Section: Neutrophil Contributions To Lymphangiogenesismentioning

confidence: 99%

Neutrophil Interactions with the Lymphatic System

Jakovija

Chtanova

2021

Cells

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The lymphatic system is a complex network of lymphatic vessels and lymph nodes designed to balance fluid homeostasis and facilitate host immune defence. Neutrophils are rapidly recruited to sites of inflammation to provide the first line of protection against microbial infections. The traditional view of neutrophils as short-lived cells, whose role is restricted to providing sterilizing immunity at sites of infection, is rapidly evolving to include additional functions at the interface between the innate and adaptive immune systems. Neutrophils travel via the lymphatics from the site of inflammation to transport antigens to lymph nodes. They can also enter lymph nodes from the blood by crossing high endothelial venules. Neutrophil functions in draining lymph nodes include pathogen control and modulation of adaptive immunity. Another facet of neutrophil interactions with the lymphatic system is their ability to promote lymphangiogenesis in draining lymph nodes and inflamed tissues. In this review, we discuss the significance of neutrophil migration to secondary lymphoid organs and within the lymphatic vasculature and highlight emerging evidence of the neutrophils’ role in lymphangiogenesis.

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Section: Neutrophil Contributions To Lymphangiogenesismentioning

confidence: 99%

Neutrophil Interactions with the Lymphatic System

Jakovija

Chtanova

2021

Cells

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“…The lymphatic system, composed of lymph nodes, lymph ducts and lymphatic vessels, plays an important role in maintaining interstitial fluid homeostasis through intestinal water and macromolecules absorption and returning them back to the bloodstream [ 1 ]. Lymphangiogenesis, the generation of new lymphatic vessels from the preexisted ones, occurs during pathological conditions including in inflammation and cancer progression [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Heteronemin Suppresses Lymphangiogenesis Through ARF-1 and MMP-9/VE-Cadherin/Vimentin

Chen

et al. 2021

Biomedicines

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Lymphatic metastasis is a biological procedure associated with the pathogenesis of several diseases, especially in tumor metastasis. Therefore, regulation of lymphangiogenesis has become a promising strategy for cancer therapy. In this study, we aimed to investigate the anti-lymphangiogenic effect of heteronemin (SP-1) isolated from the sponge Hyrtios sp. in vitro and in vivo. Human lymphatic endothelial cells (LECs) were utilized to evaluate the anti-lymphangiogenic effect of SP-1 in vitro. Molecular docking, western blotting, flow-cytometry, MTT and ELISA were performed to investigate the mechanism of action. For in vivo approaches, the transgenic (fli1:EGFP; gata1:DsRed) zebrafish and mouse ear sponges were used. Molecular docking studies showed that SP-1 is a potent vascular endothelial growth factor receptor 3 (VEGFR-3)-binding compound. Treatment of LEC with SP-1 reduced the phosphorylation of VEGFR-3. SP-1 suppressed the development of the thoracic duct in zebrafish and mouse lymphangiogenesis ear sponges in vivo. Mechanistically, SP-1 induced the cell cycle arrest of LECs in the G0/G1 phase and reduced the downstream of VEGFR-3, such as phosphorylated MEK/ERK and NF-κB. In addition, SP-1 inhibited LECs’ tubulogenesis and migration through the ARF-1 and MMP-9/VE-cadherin/vimentin. Overall, anti-lymphangiogenic properties of SP-1 occur by downregulating the VEGFR-3 cascade, ARF-1 and MMP-9/VE-cadherin/vimentin. Collectively, these results proposed that SP-1 might be a potential candidate for the treatment of lymphangiogenesis-associated diseases.

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“…In humans, the lymphatic system begins to develop between the 6th and 7th week of pregnancy, whereas in mice it appears around the embryonic day 10 (E10.0). The wellknown homeobox transcription factor Prox1 (Prospero homeobox 1) [75] and the growth factor VEGFC (Vascular endothelial growth factor C) [76] are typical LECs markers, playing a critical role in lymphatic vessels prenatal sprouting from embryonic veins and maturation [77,78]. Prox1 upregulates the expression of lymphatic-specific genes in LECs acting as a master regulatory gene leading to lymphatic commitment and maintenance [79,80].…”

Section: Lymphatic Vessels Of Airways and Lungsmentioning

confidence: 99%

Draining the Pleural Space: Lymphatic Vessels Facing the Most Challenging Task

Solari

Marcozzi

Ottaviani

et al. 2022

Biology

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Lymphatic vessels exploit the mechanical stresses of their surroundings together with intrinsic rhythmic contractions to drain lymph from interstitial spaces and serosal cavities to eventually empty into the blood venous stream. This task is more difficult when the liquid to be drained has a very subatmospheric pressure, as it occurs in the pleural cavity. This peculiar space must maintain a very low fluid volume at negative hydraulic pressure in order to guarantee a proper mechanical coupling between the chest wall and lungs. To better understand the potential for liquid drainage, the key parameter to be considered is the difference in hydraulic pressure between the pleural space and the lymphatic lumen. In this review we collected old and new findings from in vivo direct measurements of hydraulic pressures in anaesthetized animals with the aim to better frame the complex physiology of diaphragmatic and intercostal lymphatics which drain liquid from the pleural cavity.

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Mechanosensation and Mechanotransduction by Lymphatic Endothelial Cells Act as Important Regulators of Lymphatic Development and Function

Cited by 14 publications

References 226 publications

Neutrophil Interactions with the Lymphatic System

Neutrophil Interactions with the Lymphatic System

Heteronemin Suppresses Lymphangiogenesis Through ARF-1 and MMP-9/VE-Cadherin/Vimentin

Draining the Pleural Space: Lymphatic Vessels Facing the Most Challenging Task

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