Mihaela Skobe, Michael Detmar 

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Structure, Function, and Molecular Control of the Skin Lymphatic System  Mihaela Skobe, Michael Detmar  Journal of Investigative Dermatology Symposium Proceedings  Volume 5, Issue 1, Pages 14-19 (December 2000) DOI: 10.1046/j.1087-0024.2000.00001.x Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Relation between the lymphatic and blood-capillary network of the skin. Lymphatic vessels (white); arterial (red) and venous (blue) parts of the blood-capillary network. (modified afterZhdanov, 1952) Journal of Investigative Dermatology Symposium Proceedings 2000 5, 14-19DOI: (10.1046/j.1087-0024.2000.00001.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Structural features of a dermal lymphatic capillary. Lymphatic endothelial cells are firmly attached to the collagen and elastin fibers in tissues by anchoring filaments. An increase of the interstitial pressure caused by an increased fluid volume in tissue stretches the fibers and expands the lymphatic lumen. Furthermore, overlapping intercellular junctions facilitate opening of the intercellular channels, allowing easy passage of fluid and macromolecules into the vessel. (modified afterLeak, 1970) Journal of Investigative Dermatology Symposium Proceedings 2000 5, 14-19DOI: (10.1046/j.1087-0024.2000.00001.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Visualization of skin lymphatic vessels by uptake of FITC-dextrane. High-molecular weight FITC-dextrane (MW 500 000) was injected intradermally into mouse skin (10 μL of a 2% solution in 0.9 M NaCl). Skin, turned upside down, was examined 30 min after injection by using a Leica DM IRBE microscope. Lymphatic vessels (arrow) have taken up FITC-dextrane from the interstitium and exhibit bright fluorescence. Blood vessels (arrowhead) are unable to absorb the high-molecular mass dextrane and remain unlabeled. Note that the lymphatic vessel runs in parallel with a blood vessel. Journal of Investigative Dermatology Symposium Proceedings 2000 5, 14-19DOI: (10.1046/j.1087-0024.2000.00001.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Expression of the endothelial cell markers LYVE-1, PAL-E, and CD31 in the cutaneous vasculature. (A) Double immunofluorescent staining of LYVE-1 receptor (red) and PAL-E antigen (green) in 50 μm thick section of human foreskin. The stainings are mutually exclusive, indicating high specificity of the LYVE-1 receptor for lymphatics and of PAL-E for blood vessels. Note the high lymphatic vessel density. (B–D) Double immunofluorescent staining of 6 μm thick skin sections with antibodies to (B) CD31 and (C) LYVE-1; (D) overlapping image of (B) and (C). CD31 is clearly expressed in both lymphatic (arrows) and blood (arrowheads) vessels. Note that all lymphatic vessels express CD31. Dots indicate dermal–epidermal junction. Scale bar: 20 μm. Journal of Investigative Dermatology Symposium Proceedings 2000 5, 14-19DOI: (10.1046/j.1087-0024.2000.00001.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Northern blot analysis of VEGF-C mRNA (2.4 kb) expression in cultured cells derived from human skin. (1) Melanocytes; (2) keratinocytes; (3) fibroblasts; (4) microvascular endothelial cells; (5) untreated; and (6) TGFα treated human keratinocytes (100 ng/ml, 6 h). TGFα strongly upregulates expression of VEGF-C in keratinocytes. Hybridization with a β-actin probe served as a loading control. Journal of Investigative Dermatology Symposium Proceedings 2000 5, 14-19DOI: (10.1046/j.1087-0024.2000.00001.x) Copyright © 2000 The Society for Investigative Dermatology, Inc Terms and Conditions