Electron microscopic observations on lymphatic capillaries and the structural components of the connective tissue-lymph interface

Leak, Lee V.

doi:10.1016/0026-2862(70)90031-2

Cited by 196 publications

(113 citation statements)

References 35 publications

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“…It appears that the tumor cells need to penetrate the lymphatic endothelium twice to translocate into the interstitium of a lymph node. Because lymphatic vessels do not contain tight junctions or continuous basal laminae, 36 their penetration may only require tumor cell adhesion to the endothelium and transmigration through intracellular gaps that have been described to occur between lymphatic endothelial cells (reviewed in Ref. 37).…”

Section: Discussionmentioning

confidence: 99%

VEGFR-3 and Its Ligand VEGF-C Are Associated with Angiogenesis in Breast Cancer

Valtola

Salvén

Heikkilä

et al. 1999

The American Journal of Pathology

481

377

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Recently , monoclonal antibodies against the human vascular endothelial growth factor receptor VEGFR-3 were shown to provide a specific antigenic marker for lymphatic endothelium in various normal tissues. In this study we have investigated the expression of VEGFR-3 and its ligand VEGF-C in normal breast tissue and in breast tumors by immunohistochemistry. VEGFR-3 was weakly expressed in capillaries of normal breast tissue and in fibroadenomas. In intraductal breast carcinomas , VEGFR-3 was prominent in the "necklace" vessels adjacent to the basal lamina of the tumor-filled ducts. VEGF receptor 1 and 2 as well as blood vessel endothelial and basal lamina markers were colocalized with VEGFR-3 in many of these vessels. Antibodies against smooth muscle ␣-actin gave a weak staining of the necklace vessels , suggesting that they were incompletely covered by pericytes/smooth muscle cells. A highly elevated number of VEGFR-3 positive vessels was found in invasive breast cancer in comparison with histologically normal breast tissue (P < 0.0001 , the Mann-Whitney test). VEGF-C was located in the cytoplasm of intraductal and invasive cancer cells. The results demonstrate that the expression of VEGFR-3 becomes up-regulated in the endothelium of angiogenic blood vessels in breast cancer. The results also suggest that VEGF-C secreted by the intraductal carcinoma cells acts predominantly as an angiogenic growth factor for blood vessels , although this paracrine signaling network between the cancer cells and the endothelium may also be involved in modifying the permeabilities of both blood and lymphatic vessels and metastasis formation. (Am J Pathol 1999, 154:1381-1390)

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Section: Discussionmentioning

confidence: 99%

VEGFR-3 and Its Ligand VEGF-C Are Associated with Angiogenesis in Breast Cancer

Valtola

Salvén

Heikkilä

et al. 1999

The American Journal of Pathology

481

377

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“…slightly larger than an average blood capillary [7]. Measurements by Geleff et al and Sauter et al [19,48] found distances between blood and lymphatic capillaries of the order of 10 −4 m. Lymphatic capillaries are known to follow blood capillaries in close proximity around the entire body [8,30]. Given the lack of accurate three-dimensional data on real vessel geometries we opt to solve our problem over an idealized periodic geometry, displayed in Figure 2 (arrows indicate the fluid movement), in which blood and lymphatic capillaries are distributed uniformly, in a square lattice, throughout the tissue.…”

Section: Model Developmentmentioning

confidence: 99%

A Model for Interstitial Drainage Through a Sliding Lymphatic Valve

2015

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This study investigates fluid flow and elastic deformation in tissues that are drained by the primary lymphatic system. A model is formulated based on the Rossi hypothesis that states that the primary lymphatic valves, which are formed by overlapping endothelial cells around the circumferential lining of lymphatic capillaries, open in response to swelling of the surrounding tissue. Tissue deformation and interstitial fluid flow through the tissue are treated using the Biot equations of poroelasticity and, the fluid flux, (into the interstitium) across the walls of the blood capillaries, is assumed to be linearly related to the pressure difference across the walls via a constant of proportionality (the vascular permeability). The resulting model is solved in a periodic domain containing one blood capillary and one lymphatic capillary starting from a configuration in which the tissue is undeformed. On imposition of a constant pressure difference between blood and lymphatic capillaries the solutions are found to settle to a steady state. Given that the magnitude of pressure fluctuations in the lymphatic system is much smaller than this pressure difference between blood and lymph it is postulated that the resulting steady state solution gives a good representation of the state of the tissue under physiological conditions. The effects of changes to the Young's modulus of the tissue, the blood-lymphatic pressure difference, vascular permeability and valve dimensions on the steady state are investigated and discussed in terms of their effects on oedema in the context of age-and pregnancy-related changes to the body.

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“…The observation in the present study and those of other workers (24,29) suggest that particulate materials are able to cross the pulmonary epithelium within vesicles to gain entrance into the pulmonary interstitium. This removal of fluids and proteins from the pulmonary interstitium is similar to the pattern of lymphatic drainage in other tissue (27,30,31). Therefore, fluids, particles and cells are removed from the pulmonary interstitium by way of vesicles and the clefts of intercellular junctions.…”

Section: Intravascular Injection Of Tracer Substancesmentioning

confidence: 58%

Lymphatic removal of fluids and particles in the mammalian lung.

Leak¹

1980

Environ Health Perspect

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The structure and distribution of pulmonary lymphatics and their permeability to fluids and particulate materials have been investigated in the lungs of rats following fixation by combined intratracheal and vascular perfusion. In such preparations, the lymphatics remain in a distended state, and a close relationship to other structural components of the pulmonary interstitium is maintained. They were identified in regions with an abundant amount of connective tissue, forming an elaborate plexus within the pleura, the interlobular septum, peribronchial and perivascular areas. Recent data have shown that water-soluble molecules and particulate matter are removed from the interstitium along the lymphatic capillary (initial lymphatics) segment. It is distinguished by attenuated endothelial cells with extensively overlapping cell margins which are easily separated. We have studied this segment of the lymphatic vascular system following intratracheal injections of colloidal particles (ferritin and carbon) to determine the structural features responsible for the transport of large molecules and particulate materials across the lymphatic endothelial wall in the lung. The results showed that the tracer particles cross the lymphatic endothelial wall via the clefts of intercellular junctions. While the tracer particles were observed within vesicles, the question oftransport across the lymphatic endothelium via plasmalemmal vesicles is still not settled since the number and size of vesicles containing tracer particles also increased with time. Intravascular injected dextran was also localized within the clefts of intercellular junctions and plasmalemmal vesicles. The results obtained with intratracheal and intravascular injected tracer substances are consistent with those observed in lymphatic capillaries for other tissues.

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Electron microscopic observations on lymphatic capillaries and the structural components of the connective tissue-lymph interface

Cited by 196 publications

References 35 publications

VEGFR-3 and Its Ligand VEGF-C Are Associated with Angiogenesis in Breast Cancer

VEGFR-3 and Its Ligand VEGF-C Are Associated with Angiogenesis in Breast Cancer

A Model for Interstitial Drainage Through a Sliding Lymphatic Valve

Lymphatic removal of fluids and particles in the mammalian lung.

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