Lymphatic Dysfunction, Leukotrienes, and Lymphedema

Jiang, Xinguo; Nicolls, Mark R.; Tian, Wen; Rockson, Stanley G.

doi:10.1146/annurev-physiol-022516-034008

Cited by 96 publications

(94 citation statements)

References 142 publications

(174 reference statements)

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“…Tumor cells were identified entering initial lymphatics by using chemokine gradient guidance via open junction, leading to distant metastasis of primary tumors. The LVs are essential for trafficking of immune cells and soluble antigens from peripheral tissues to draining lymph nodes [22]. The basic function of lymph is to remove pathogens that invade tissues.…”

Section: Lvs Serve As a Bridge Between Innate And Adaptive Immunitymentioning

confidence: 99%

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Pei

Zeng

et al. 2020

Kidney Dis

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Background: Lymphatic vessels transport lymph away from microvascular beds into the cardiovascular system. The basic function of the lymphatic system include absorption of wa ter and macromolecules in the interstitial fluid, which plays an important role in maintaining osmotic balance of the body. Recent studies have shown that lymphangiogenesis is associated with tumor metabolism, injury repair, and chron ic inflammation, and deteriorates disease progression via immune cell trafficking. Summary: Renal interstitial lymph angiogenesis is found in patients with chronic kidney dis ease and a series of animal models of renal fibrosis. Lymphat ic vessels transfer antigen and antigenpresenting cells from peripheral tissues to lymph nodes, which initiates adaptive immunity and in turn deteriorates renal inflammation and renal fibrosis, even in nonautoimmune renal diseases. Key Messages: This review summarizes the latest findings on how lymphatics participate in the progression of chronic kid ney disease. This discussion will serve to highlight the role of adaptive immunity in noninfectious and nonautoimmune nephropathy, in order to provide new ideas and methods for prevention and treatment of kidney diseases.

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Section: Lvs Serve As a Bridge Between Innate And Adaptive Immunitymentioning

confidence: 99%

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Pei

Zeng

et al. 2020

Kidney Dis

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“…Indeed, we found that the limbal lymphatics are directly connected to the conjunctival lymphatics through multiple short lymphatics present along the corneal edge ( Fig.1Q-U). We also detected the Prox1 -high luminal valves in mature limbal lymphatics in adults ( Fig.1R,S), suggesting non-capillary characters of limbal lymphatics (2,40). Together, the ocular lymphatics and Schlemm's canal display distinct anatomic and molecular characteristics.…”

Section: Visualization Of the Ocular Surface Lymphatic Vessels And Scmentioning

confidence: 64%

Organogenesis and Distribution of the Ocular Lymphatic Vessels in the Anterior Eye: Implication to Glaucoma Surgery Site Selection

et al. 2019

Preprint

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Glaucoma surgeries, such as trabeculectomy, are performed to lower the intraocular pressure to reduce the risk of vision loss. The surgeries create a new passage in the eye that reroutes the aqueous humor outflow to the subconjunctival space, where the fluid is presumably absorbed by the conjunctival lymphatics. However, the current knowledge of these ocular surface lymphatics remains limited. Here, we characterized the biology and function of the ocular lymphatics using transgenic lymphatic reporter mice and rats. We found that the limbal and conjunctival lymphatic networks are progressively formed by a primary lymphatic vessel that grows out from the nasal-side medial canthus region at the time of birth. This primary lymphatic vessel immediately branches out and invades the limbus and conjunctiva, and then simultaneously encircles the cornea in a bidirectional manner. As a result, the distribution of the ocular lymphatic is significantly polarized toward the nasal side, and the limbal lymphatics are directly connected to the conjunctival lymphatics. New lymphatic spouts are mainly produced from the nasal-side limbal lymphatics, posing the nasal side of the eye more responsive to fluid drainage and inflammatory stimuli. Consistently, when a fluorescent tracer was injected, fluid clearance was much more efficient in the nasal side than the temporal side of the eyes. In comparison, blood vessels are evenly distributed on the front surface of the eyes. We found that these distinct vascular distribution patterns were also conserved in human eyes. Together, our study demonstrated that the ocular surface lymphatics are more densely present in the nasal side and uncovered the potential clinical benefits in selecting the nasal side as a surgical site for glaucoma surgeries to improve the fluid drainage.

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“…As with angiogenesis, there are also other growth factors, such as FGF-2 [16], PDGF [17], angiopoietin [18,19] and HGF [20], that induce lymphangiogenesis. Moreover, in a wide range of diseases, such as cancer, cardiovascular disease, and inflammation, pro-inflammatory or anti-inflammatory cytokines may induce or suppress lymphangiogenesis [21,22]. Pro-inflammatory cytokines, like interleukin (IL)-1, IL-12, IL-18, tumor necrosis factor (TNF)-α, and interferon (IFN)-β, are produced mainly by macrophages but also by NK cells, T cells, B cells and neutrophils [23,24].…”

Section: Endogenous Regulators Of (Lymph)angiogenesismentioning

confidence: 99%

Role of Endogenous Regulators of Hem- And Lymphangiogenesis in Corneal Transplantation

Clahsen

Büttner

Hatami

et al. 2020

JCM

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Under normal conditions, the cornea, being the transparent "windscreen" of the eye, is free of both blood and lymphatic vessels. However, various diseases of the eye, like infections, can interfere with the balance between promoting and inhibiting factors, which leads to ingrowth of blood and lymphatic vessels. The newly formed lymphatic vessels increase the risk of graft rejection after subsequent corneal transplantation. Corneal transplantation is one of the most commonly performed transplantations worldwide, with more than 40,000 surgeries per year in Europe. To date, various anti-hem-and anti-lymphangiogenic treatment strategies have been developed specifically for the corneal vascular endothelial growth factor (VEGF) pathway. Currently, however, no treatment strategies are clinically available to specifically modulate lymphangiogenesis. In this review, we will give an overview about endogenous regulators of hem-and lymphangiogenesis and discuss potential new strategies for targeting pathological lymphangiogenesis. Furthermore, we will review recently identified modulators and demonstrate that the cornea is a suitable model for the identification of novel endogenous modulators of lymphangiogenesis. The identification of novel modulators of lymphangiogenesis and a better understanding of the signaling pathways involved will contribute to the development of new therapeutic targets for the treatment of pathological lymphangiogenesis. This, in turn, will improve graft rejection, not only for the cornea.

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Lymphatic Dysfunction, Leukotrienes, and Lymphedema

Cited by 96 publications

References 142 publications

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Organogenesis and Distribution of the Ocular Lymphatic Vessels in the Anterior Eye: Implication to Glaucoma Surgery Site Selection

Role of Endogenous Regulators of Hem- And Lymphangiogenesis in Corneal Transplantation

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