title: Distinct molecular composition of blood and lymphatic vascular endothelial cell junctions establishes specific functional barriers within the peripheral lymph node.
abstract: Lymph nodes are strategically localized at the interfaces between the blood and lymphatic vascular system, delivering immune cells and antigens to the lymph node. As cellular junctions of endothelial cells actively regulate vascular permeability and cell traffic, we have investigated their molecular composition by performing an extensive immunofluorescence study for adherens and tight junction molecules, including vascular endothelium (VE)-cadherin, the vascular claudins 1, 3, 5 and 12, occludin, members of the junctional adhesion molecule family plus endothelial cell-selective adhesion molecule (ESAM)-1, platelet endothelial cell adhesion molecule-1, ZO-1 and ZO-2. We found that junctions of high endothelial venules (HEV), which serve as entry site for naive lymphocytes, are unique due to their lack of the endothelial cell-specific claudin-5. LYVE-1(+) sinus-lining endothelial cells form a diffusion barrier for soluble molecules that arrive at the afferent lymph and use claudin-5 and ESAM-1 to establish characteristic tight junctions. Analysis of the spatial relationship between the different vascular compartments revealed that HEV extend beyond the paracortex into the medullary sinuses, where they are protected from direct contact with the lymph by sinus-lining endothelial cells. The specific molecular architecture of cellular junctions present in blood and lymphatic vessel endothelium in peripheral lymph nodes establishes distinct barriers controlling the distribution of antigens and immune cells within this tissue.
authors.affiliation: Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Friederike
authors.initials: F
authors.lastname: Pfeiffer
authors.forename: Varsha
authors.initials: V
authors.lastname: Kumar
authors.forename: Stefan
authors.initials: S
authors.lastname: Butz
authors.forename: Dietmar
authors.initials: D
authors.lastname: Vestweber
authors.forename: Beat A
authors.initials: BA
authors.lastname: Imhof
authors.forename: Jens V
authors.initials: JV
authors.lastname: Stein
authors.forename: Britta
authors.initials: B
authors.lastname: Engelhardt
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000032:analysis; D002465:Cell Movement; D042783:Endothelial Cells / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D004729:Endothelium, Lymphatic / Q000166:cytology*; D005260:Female; D017629:Gap Junctions / Q000737:chemistry*; D007136:Immunoglobulins; D008198:Lymph Nodes / Q000098:blood supply* / Q000502:physiology* / Q000648:ultrastructure; D042601:Lymphatic Vessels / Q000737:chemistry; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D014699:Venules / Q000502:physiology; D062765:Junctional Adhesion Molecule B
chemical_list: D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C428190:Esam protein, mouse; C498781:Jam2 protein, mouse; D062765:Junctional Adhesion Molecule B