Contractile Physiology of Lymphatics

Zawieja, David C.

doi:10.1089/lrb.2009.0007

Cited by 294 publications

(338 citation statements)

References 79 publications

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“…They report fewer smooth muscle cells in the valve sinus region compared to upstream and downstream segments. 2,7 However, we observed no significant changes in the average collagen or elastin layer thickness across these regions of the lymphangion. The only change we observed was a decrease in elastin layer thickness with increasing pressure (from 2 to 7 cmH 2 O), which is indicative of the incompressible nature of the vessel.…”

Section: Discussionmentioning

confidence: 51%

“…This result parallels the relatively homogeneous distribution of collagen and elastin observed from the NLOM images. However, given the inhomogeneous distribution of muscle cells in a lymphangion, 2,7 there could be regional differences in the active pressure-diameter response of the vessel. Furthermore, there may be differences in the extent of lymphangion regional variation between mesenteric lymphatics and larger collecting ducts (e.g., thoracic duct) and even more variation between species.…”

Section: Discussionmentioning

confidence: 99%

“…Recent work has shown that muscle cells are distributed nonhomogeneously in the vessel wall. 1,2,6,7 Collagen and elastin are the other dominant components of the vessel wall. 8,9 However, past studies of the ultrastructure of the lymphatic vessel largely ignored the mechanical properties of the vessel wall.…”

Section: Introductionmentioning

confidence: 99%

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Passive Pressure–Diameter Relationship and Structural Composition of Rat Mesenteric Lymphangions

Rahbar

Weimer

Gibbs

et al. 2012

Lymphatic Research and Biology

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Background: Lymph flow depends on both the rate of lymph production by tissues and the extent of passive and active pumping. Here we aim to characterize the passive mechanical properties of a lymphangion in both midlymphangion and valve segments to assess regional differences along a lymphangion, as well as evaluating its structural composition. Methods and Results: Mesenteric lymphatic vessels were isolated and cannulated in a microchamber for pressure-diameter (P-D) testing. Vessels were inflated from 0 to 20 cmH 2 O at a rate of 4 cmH 2 O/min, and vessel diameter was continuously tracked, using an inverted microscope, video camera, and custom LabVIEW program, at both mid-lymphangion and valve segments. Isolated lymphatic vessels were also pressure-fixed at 2 and 7 cmH 2 O and imaged using a nonlinear optical microscope (NLOM) to obtain collagen and elastin structural information. We observed a highly nonlinear P-D response at low pressures (3-5 cmH 2 O), which was modeled using a three-parameter constitutive equation. No significant difference in the passive P-D response was observed between mid-lymphangion and valve regions. NLOM imaging revealed an inner elastin layer and outer collagen layer at all locations. Lymphatic valve leaflets were predominantly elastin with thick axially oriented collagen bands at the insertion points. Conclusions: We observed a highly nonlinear P-D response at low pressures (3-5 cmH 2 O) and developed the first constitutive equation to describe the passive P-D response for a lymphangion. The passive P-D response did not vary among regions, in agreement with the composition of elastin and collagen in the lymphatic wall.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 99%

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Passive Pressure–Diameter Relationship and Structural Composition of Rat Mesenteric Lymphangions

Rahbar

Weimer

Gibbs

et al. 2012

Lymphatic Research and Biology

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“…Lymphatic vessels were first discovered in the gut as they turned milky white after a meal; we now appreciate this "chyle" as dietary lipids that are taken up specifically by the lymphatics, and some laboratories are focused on targeting this component for oral drug delivery to avoid first-pass metabolism in the liver (12). Vascular and microcirculatory physiologists have traditionally focused on the fluid and solute transport functions of the lymphatic system and its relation to blood capillaries and the interstitial space (13), as well as the regulation of pump function by the collecting lymphatic vessels (14). Tumor biologists have pieced together the molecular regulators of lymphangiogenesis by tumor cells and inflammatory leukocytes in the tumor microenvironment (1, 2), whereas immunologists have traditionally considered mostly the anatomic aspects of the lymphatic system, whereby lymphatic vessels serve to transport leukocytes and antigens to the lymph node, where cell-cell interactions regulate adaptive immune responses (15,16).…”

Section: Lymphatic Vessels and Cancer Progressionmentioning

confidence: 99%

Immunomodulatory Roles of Lymphatic Vessels in Cancer Progression

Swartz

2014

Cancer Immunology Research

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Lymphatic vessels in the tumor microenvironment are known to foster tumor metastasis in many cancers, and they can undergo activation, hyperplasia, and lymphangiogenesis in the tumor microenvironment and in the tumor-draining lymph node. The mechanism underlying this correlation was originally considered as lymphatic vessels providing a physical route for tumor cell dissemination, but recent studies have highlighted new roles of the lymphatic endothelium in regulating host immunity. These include indirectly suppressing T-cell function by secreting immunosuppressive factors and inhibiting dendritic cell (DC) maturation, as well as directly driving Tcell tolerance by antigen presentation in the presence of inhibitory ligands.

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“…These capillaries drain into precollecting and collecting vessels that have continuous, "zipper-like" interendothelial junctions [30] and are surrounded by smooth muscle. Collecting vessels are organized into contractile segments called lymphangions, separated by bileaflet valves, that create the driving force for unidirectional lymph propulsion [30,31,[34][35][36]. Collecting lymphatic vessels that carry lymph to and from the lymph nodes are referred to as afferent and efferent lymphatic vessels, respectively.…”

Section: Lymphatic Physiology and Neogenesismentioning

confidence: 99%

Role of Lymphatic Vessels in Tumor Immunity: Passive Conduits or Active Participants?

Lund

Swartz

2010

J Mammary Gland Biol Neoplasia

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Research in lymphatic biology and cancer immunology may soon intersect as emerging evidence implicates the lymphatics in the progression of chronic inflammation and autoimmunity as well as in tumor metastasis and immune escape. Like the blood vasculature, the lymphatic system comprises a highly dynamic conduit system that regulates fluid homeostasis, antigen transport and immune cell trafficking, which all play important roles in the progression and resolution of inflammation, autoimmune diseases, and cancer. This review presents emerging evidence that lymphatic vessels are active modulators of immunity, perhaps fine-tuning the response to adjust the balance between peripheral tolerance and immunity. This suggests that the tumor-associated lymphatic vessels and draining lymph node may be important in tumor immunity which in turn governs metastasis.

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Contractile Physiology of Lymphatics

Cited by 294 publications

References 79 publications

Passive Pressure–Diameter Relationship and Structural Composition of Rat Mesenteric Lymphangions

Passive Pressure–Diameter Relationship and Structural Composition of Rat Mesenteric Lymphangions

Immunomodulatory Roles of Lymphatic Vessels in Cancer Progression

Role of Lymphatic Vessels in Tumor Immunity: Passive Conduits or Active Participants?

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