The Endothelium in the Lymph Nodes

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Lymph nodes are interconnected in collectors and are controlling stations for the lymph fluid. Their number is estimated as 600 to 700; morphology and size are variable. Lymph nodes are encapsulated structures and incompletely subdivided by trabecules, between which a cellular network exists containing white blood cells. These can react to antigens via humoral and cellular immune responses, and small particles in the lymph are eliminated as well. Lymph nodes consist of a cortical zone (B-cell zone with primary and secondary follicles), a paracortical zone (T-cell zone), and a medullary region. Vasa afferentia lead the primary lymph to the marginal sinus; from there it runs through the trabecular sinus via intermediary sinus into the medullary sinus, draining to vasa efferentia. An exact and complete description of the endothelium of the lymphatic parts of the lymph nodes does not yet exist. The marginal sinus possesses a morphology similar to that of the precollectors. The intermediary lymph sinus endothelium has gaps so that the lymph fluid can be in contact with the reticular cells of the lymph node. Additional lymph nodes can concentrate the lymph proteins three- to fourfold. In the lumen of the lymphatics of the lymph node, preferentially macrophages (particularly in the medullary sinus), a variable number of erythrocytes, neu-trophils, lymphocytes, and plasma cells occur.


Anchoring filaments: A characteristic feature of initial lymphatic vessels. They connect the abluminal membrane of endothelial cells to the surrounding elastic fibers. The main molecular component is fibrillin.

Basement membrane: Extracellular matrix characteristically found under epithelial cells. There are two distinct layers: the basal lamina, immediately adjacent to the cells, is a product of the epithelial cells themselves and contains collagen type IV and the reticular lamina is produced by fibroblasts of the underlying connective tissue and contains fibrillar collagen.

Caveolae: Small invaginations of the plasma membrane in many cell types, especially in endothelial cells. These flask-shaped structures are rich in proteins and lipids and are used for several functions in signal transduc-tion (Anderson, 1998) They are also believed to play a role in endocytosis, oncogenesis, and the uptake of pathogenic bacteria.

Connective tissue: Any type of biological tissue with an extensive extracellular matrix. There are several basic types. Loose connective tissue holds organs and epithelia in place, and has a variety of proteinaceous fibers, including collagen and elastin.

Dense peripheral band (DPB): Dense 150-300 nm broad band, following the circumference of the cell, built up by cytoskeletal filaments (mostly actin-filaments).

Elastic fibers: Fibers which are capable of returning to their original length after being stretched. The protein molecules which compose these fibers are synthesized in fibroblasts and smooth muscle cells. They are not found in bundles but occur as solitary fibers.

Elementary form: Very simple formation of cell-cell-connection, without any peculiarities. Vertical contact zone between two cells.

Filaments: Cytoskeletal elements like intermediate filaments, thin actin filaments and microtubules. Frequently the three components work together to enhance both structural integrity, cell shape, and cell and organelle motility.

Multifold system: Cell-cell-connection with interdigitating structure.

Nucleus: Largest cell organelle, found in the majority of eukaryotic cells, which contains most of the cell's genetic material. Nuclei have two primary functions: to control chemical reactions within the cytoplasm and to store information needed for cellular division.

Open-interface formations: Pressure relief valve with direct connection between tissue channels and initial lymphatics.

Open-junction formations: Cell borders of neighboring cells overlap one another, thus forming inlet valves.

Shapes of endothelial cells: Initial lymphatics possesses the circumference similar to an oak leaf.

Simple overlap: Cell-cell-connection. The apical part of one cell is connected with the basal part of another cell

Single fold: Cell-cell-connection. The cell border of one cell digitates into the neighboring cell border like a finger in an inprint.

Sproutlike formations: Bud-like cell formation, extended from an initial lymphatic, consisting of circularly arranged spindle-shaped endothelial cells.

Tissue channels: 1% of extracellular matrix, containing free fluid otherwise bound on the gelatinous phase.

Trabecular and valvelike structures: Trabecular structure: spindle-shaped modified endothelial cells, based in the endothelium and running through the lumen to connect with an endothelial cell in an opposite position. Valvelike structure: spindle-shaped modified endothelial cells, forming a ridge, acting as uncompleted valve.

Vesicles and invaginations: Vesicles are relatively small and enclosed cell compartments, separated from the cytosol by at least one lipid bilayer. Vesicles store, transport, or digest cellular products and wastes. Invaginations are the folding in of the plasmalemma so as to form a pocket in the surface (surface vesicle).


1. Drinker and Field (1933).

2. Drinker and Yoffey (1941).

3. Yoffey and Courtice (1970).

4. Rusznyak, Foldi, and Szabo (1969).

5. Wong and Gottlieb (1986).

8. Mislin and Rathnow (1961).

Further Reading

Azzali, G. (1992). Morphological features of absorbing peripheral lymphatic vessels studied by TEM, SEM, and three-dimensional models. In

Scanning Electron Microscopy of Vascular Casts: Methods and Applications, pp. 83-98. Dordrecht: Kluwer Academic.

Cahill, R. N. P., Wayne, W. G., and Hay, J. B. (2001). Lymphatic system. In Encyclopedia of Life Sciences. Nature publishing group: A good overview, easily obtained on the Internet.

Castenholz, A. (1998). Functional microanatomy of initial lymphatics with special consideration of the extracellular matrix. Lymphology 31(3), 101-118. This study is based on scanning electron microscopy and con-focal laser scanning microscopy and gives insights into the architecture of the fibrous network of the extracellular matrix and its functional features. The author proposes a concept that considers the histomechanics of the initial lymphatics with the surrounding connective fiber tissue describing the structural basis for the permeability of the lymphatic vascular wall.

Foldi, M., and Casley-Smith, J. R. (eds.) (1983). Lymphangiology. Stuttgart: Schattauer. The aim of this book is to build bridges between basic scientists, radiologists, and clinicians. It is a classical handbook with more than 800 pages. Themes of the first ten chapters are phy-logeny; structure and functioning of the blood vessels, interstitial tissues, and lymphatics; the lymphangion; enzymes in lymph; insufficiency of lymph flow; general pathology of the lymph vascular system; injury and the lymphatic system; the lymphatic system in burns; and special pathology of the lymph vascular system with anatomical, physiological, and pathological aspects. Twelve chapters deal with anatomy, physiology, pathophysiology, and therapy of special organs. Further chapters are concerned with lymphedema; surgical therapy for lymphedema; pharmacology of the lymphatics; nuclear medicine techniques; thoracic duct cannulation; lymphatic filariasis; malformation of the lymphatic system; and pediatric lymphangiology. It seems to be the most actual book on these issues about the lymphatic system in English. In German the 5th edition of Lehrbuch der Lymphologie, by Foldi, M., and Kubik, S., was published in 2002 (Manchen: Urban & Fischer ISBN: 3-437-45321-1).

Gerli, R., Solito, R., Weber, E., and Agliano M. (2000). Specific adhesion molecules bind anchoring filaments and endothelial cells in human skin initial lymphatics. Lymphology 33(4), 148-157. Anchoring filaments connect the abluminal membrane of endothelial cells to the surrounding elastic fibers and possibly enable transmission of chemical and/or mechanical stimuli from the extracellular matrix to the endothelial cells. So they could contribute to the initial formation of lymph.

Kato, S. (2000). Organ specificity of the structural organization and fine distribution of lymphatic capillary networks. Histochemical study. Histol. Histopathol. 15, 185-197. The histochemical method of analyzing the topography of lymphatics. The lymphatics and blood vessels are characterized by an enzyme-histochemical method and the results are discussed in relation to their ability to demonstrate the organ specificity of vascular networks under normal and pathological conditions.

Pepper, M. S. (2001). Lymphangiogenesis and tumor metastasis. Clin. Cancer Res. 7, 462-468.

Podgrabinska, S., Braun, P., Velasco, P., Kloos, B., Pepper, M. S., Jackson, D. G., and Skobe, M. (2002). Molecular characterization of lymphatic endothelial cells. Proc. Natl. Acad. Sci. USA 99, 16069-16074. Immunoselection of primary lymphatic and blood microvascular endothelial cells from human skin with the lymphatic marker LYVE-1. Description and classification of the differently expressed genes into functional groups. The characteristic gene expression profile of human lymphatic microvascular endothelial cells indicates a more active role of lymphatic endothelium in uptake and transport of molecules than previously anticipated.

Schmidt-Schönbein, G. W. (1990). Microlymphatics and lymph flow. Physiol. Rev. 70, 987-1028. Review of the morphological and physiological basis of lymph production and lymph transport. Description of the mechanism that causes expansion and compression of the initial lymphatics.

Zöltzer, H. (2003). Initial lymphatics—morphology and function of the endothelial cells. Lymphology 36, 7-25. Lymph formation usually is considered as a passive process. The cells of the initial lymphatics, however, hold a key position in absorbing fluid from the interstitial space. This study suggests that the forming and closing of the open-junction formations is an active component of the lymphatic endothelium.

Capsule Biography

Dr. Zoltzer has been engaged in lymphological research since 1985. He is head of the working group "Theoretical Lymphology" of the German Association of Lymphology (DGL).

Section I


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