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

Lund, Amanda W.; Swartz, Melody A.

doi:10.1007/s10911-010-9193-x

Cited by 36 publications

(32 citation statements)

References 134 publications

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“…In fact, it is becoming apparent that NO is a primary mechanism used by lymphatics to regulate flow. Specifically, immune cells have been shown to release NO as a mechanism for manipulating lymphatic flow as part of a local immune modulatory response to inflammation (9,25,38,41). Also, transient changes in wall shear stress (WSS) on lymphatics lead to NO release as a means of either promoting vasodilation and reducing vascular resistance to flow during sustained WSS or possibly transiently increasing the vessel diameter as a regulatory mechanism for lymphatic pumping (8,9,24).…”

Section: Discussionmentioning

confidence: 99%

Minimally invasive method for determining the effective lymphatic pumping pressure in rats using near-infrared imaging

Nelson

Akin

Weiler

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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The ability to quantify collecting vessel function in a minimally invasive fashion is crucial to the study of lymphatic physiology and the role of lymphatic pump function in disease progression. Therefore, we developed a highly sensitive, minimally invasive research platform for quantifying the pumping capacity of collecting lymphatic vessels in the rodent tail and forelimb. To achieve this, we have integrated a near-infrared lymphatic imaging system with a feedback-controlled pressure cuff to modulate lymph flow. After occluding lymphatic flow by inflating a pressure cuff on the limb or tail, we gradually deflate the cuff while imaging flow restoration proximal to the cuff. Using prescribed pressure applications and automated image processing of fluorescence intensity levels in the vessels, we were able to noninvasively quantify the effective pumping pressure (P(eff), pressure at which flow is restored after occlusion) and vessel emptying rate (rate of fluorescence clearance during flow occlusion) of lymphatics in the rat. To demonstrate the sensitivity of this system to changes in lymphatic function, a nitric oxide (NO) donor cream, glyceryl trinitrate ointment (GTNO), was applied to the tails. GTNO decreased P(eff) of the vessels by nearly 50% and the average emptying rate by more than 60%. We also demonstrate the suitability of this approach for acquiring measurements on the rat forelimb. Thus, this novel research platform provides the first minimally invasive measurements of P(eff) and emptying rate in rodents. This experimental platform holds strong potential for future in vivo studies that seek to evaluate changes in lymphatic health and disease.

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Section: Discussionmentioning

confidence: 99%

Minimally invasive method for determining the effective lymphatic pumping pressure in rats using near-infrared imaging

Nelson

Akin

Weiler

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Thus interstitial flow appears to have important functional consequences on both the lymphatic vessels as well as the draining lymph nodes, implying key roles for flow in modulating immunity in secondary lymphoid organs. And although it is fascinating to consider, the role of altered lymph flow into the tumordraining lymph node on tumor immunity has yet to be elucidated (275).…”

Section: Lymphatic Functionmentioning

confidence: 99%

Interstitial Fluid and Lymph Formation and Transport: Physiological Regulation and Roles in Inflammation and Cancer

Wiig

Swartz²

2012

Physiological Reviews

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562

574

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The interstitium describes the fluid, proteins, solutes, and the extracellular matrix (ECM) that comprise the cellular microenvironment in tissues. Its alterations are fundamental to changes in cell function in inflammation, pathogenesis, and cancer. Interstitial fluid (IF) is created by transcapillary filtration and cleared by lymphatic vessels. Herein we discuss the biophysical, biomechanical, and functional implications of IF in normal and pathological tissue states from both fluid balance and cell function perspectives. We also discuss analysis methods to access IF, which enables quantification of the cellular microenvironment; such methods have demonstrated, for example, that there can be dramatic gradients from tissue to plasma during inflammation and that tumor IF is hypoxic and acidic compared with subcutaneous IF and plasma. Accumulated recent data show that IF and its convection through the interstitium and delivery to the lymph nodes have many and diverse biological effects, including in ECM reorganization, cell migration, and capillary morphogenesis as well as in immunity and peripheral tolerance. This review integrates the biophysical, biomechanical, and biological aspects of interstitial and lymph fluid and its transport in tissue physiology, pathophysiology, and immune regulation.

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“…3,4 This LN lymphangiogenesis is thought to be important for lymph and antigen delivery to LNs, 3,5 and it also can modify immune responses. 6,7 The lymphatic endothelium normally is a minor component of LNs, so that it has been challenging to purify enough of these cells to investigate their function. Lymphatic endothelial cells (LEC) have been enriched from dermis 8,9 by cell sorting and column purification techniques, which can be a costly approach.…”

Section: Introductionmentioning

confidence: 99%

Culturing Purifies Murine Lymph Node Lymphatic Endothelium

Jordan-Williams

Ruddell

2014

Lymphatic Research and Biology

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Background: Lymph node (LN) lymphatic sinuses transport lymph, cells, and antigens from the periphery through the LN. The lymphatic endothelium lining these sinuses appears to be an important contributor to the lymph node immune response. It has been challenging to obtain sufficient LN lymphatic endothelial cells for investigation of their functions, as they are minor constituents of LNs. Methods and Results: A procedure was developed to purify lymphatic endothelial cells (LEC) from murine LNs, which yields large numbers of primary LN LEC. Two-dimensional in vitro cultures of dissociated LN stromal cells initially consist of multiple cell types, and then rapidly evolve to produce pure cultures of lymphatic endothelium within a few passages. One million LEC can be harvested after 4 weeks of culture, and much larger cell numbers can be obtained by continued culturing over long periods. The LEC cultures maintain endothelial morphology and expression of LEC markers, and preserve the same slow growth characteristics over at least 20 passages. The LEC cultures readily form tubes in Matrigel at early and at late passages, resembling those formed by LEC lines. Conclusions: A simple and economical approach to obtain purified primary murine LN LEC was developed for in vitro studies of their function. The morphology, growth characteristics, and functional behavior of these cells in tube formation assays did not change between initial and long-term passages. Large numbers of these cells can be harvested after long-term passage, so that they can be studied in biochemical and biological assays.

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

Cited by 36 publications

References 134 publications

Minimally invasive method for determining the effective lymphatic pumping pressure in rats using near-infrared imaging

Minimally invasive method for determining the effective lymphatic pumping pressure in rats using near-infrared imaging

Interstitial Fluid and Lymph Formation and Transport: Physiological Regulation and Roles in Inflammation and Cancer

Culturing Purifies Murine Lymph Node Lymphatic Endothelium

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