scholarly journals Mannose Receptor Is a Novel Ligand for L-Selectin and Mediates Lymphocyte Binding to Lymphatic Endothelium

2001 ◽  
Vol 194 (8) ◽  
pp. 1033-1042 ◽  
Author(s):  
Heikki Irjala ◽  
Eva-Liz Johansson ◽  
Reidar Grenman ◽  
Kalle Alanen ◽  
Marko Salmi ◽  
...  
Keyword(s):  
Lymphatic Vessels ◽  
Mannose Receptor ◽  
The Other ◽  
Lymphoid Tissues ◽  
Lymphatic Endothelium ◽  
Peripheral Lymph Node ◽  
High Endothelial Venules ◽  
Receptor Ligand ◽  
Peripheral Lymph ◽  
Lymphatic Organs

Continuous lymphocyte recirculation between blood and lymphoid tissues forms a basis for the function of the immune system. Lymphocyte entrance from the blood into the tissues has been thoroughly characterized, but mechanisms controlling lymphocyte exit from the lymphoid tissues via efferent lymphatics have remained virtually unknown. In this work we have identified mannose receptor (MR) on human lymphatic endothelium and demonstrate its involvement in binding of lymphocytes to lymphatic vessels. We also show that the binding requires L-selectin, and L-selectin and MR form a receptor–ligand pair. On the other hand, L-selectin binds to peripheral lymph node addressins (PNAds) on high endothelial venules (HEVs) that are sites where lymphocytes enter the lymphatic organs. Interestingly, MR is absent from HEVs and PNAds from lymphatic endothelium. Thus, lymphocyte L-selectin uses distinct ligand molecules to mediate binding at sites of lymphocyte entrance and exit within lymph nodes. Taken together, interaction between L-selectin and MR is the first molecularly defined mechanism mediating lymphocyte binding to lymphatic endothelium.

scholarly journals The influence of afferent lymphatic vessel interruption on vascular addressin expression.

1991 ◽  
Vol 115 (1) ◽  
pp. 85-95 ◽  
Author(s):  
R E Mebius ◽  
P R Streeter ◽  
J Brevé ◽  
A M Duijvestijn ◽  
G Kraal
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Lymphatic Vessel ◽  
Lymphatic Vessels ◽  
Lymphoid Tissues ◽  
Peripheral Lymph Node ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Peripheral Lymph

Tissue-selective lymphocyte homing is directed in part by specialized vessels that define sites of lymphocyte exit from the blood. These vessels, the post capillary high endothelial venules (HEV), are found in organized lymphoid tissues, and at sites of chronic inflammation. Lymphocytes bearing specific receptors, called homing receptors, recognize and adhere to their putative ligands on high endothelial cells, the vascular addressins. After adhesion, lymphocytes enter organized lymphoid tissues by migrating through the endothelial cell wall. Cells and/or soluble factors arriving in lymph nodes by way of the afferent lymph supply have been implicated in the maintenance of HEV morphology and efficient lymphocyte homing. In the study reported here, we assessed the influence of afferent lymphatic vessel interruption on lymph node composition, organization of cellular elements; and on expression of vascular addressins. At 1 wk after occlusion of afferent lymphatic vessels, HEV became flat walled and expression of the peripheral lymph node addressin disappeared from the luminal aspect of most vessels, while being retained on the abluminal side. In addition, an HEV-specific differentiation marker, defined by mAb MECA-325, was undetectable at 7-d postocclusion. In vivo homing studies revealed that these modified vessels support minimal lymphocyte traffic from the blood. After occlusion, we observed dramatic changes in lymphocyte populations and at 7-d postsurgery, lymph nodes were populated predominantly by cells lacking the peripheral lymph node homing receptor LECAM-1. In addition, effects on nonlymphoid cells were observed: subcapsular sinus macrophages, defined by mAb MOMA-1, disappeared; and interdigitating dendritic cells, defined by mAb NLDC-145, were dramatically reduced. These data reveal that functioning afferent lymphatics are centrally involved in maintaining normal lymph node homeostasis.

scholarly journals The human peripheral lymph node vascular addressin is a ligand for LECAM-1, the peripheral lymph node homing receptor.

1991 ◽  
Vol 114 (2) ◽  
pp. 343-349 ◽  
Author(s):  
E L Berg ◽  
M K Robinson ◽  
R A Warnock ◽  
E C Butcher
Keyword(s):  
Lymph Node ◽  
Lymphoid Tissues ◽  
Dependent Manner ◽  
Peripheral Lymph Node ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Homing Receptor ◽  
Calcium Dependent ◽  
Lymph Node Homing ◽  
Peripheral Lymph

The trafficking of lymphocytes from the blood and into lymphoid organs is controlled by tissue-selective lymphocyte interactions with specialized endothelial cells lining post capillary venules, in particular the high endothelial venules (HEV) found in lymphoid tissues and sites of chronic inflammation. Lymphocyte interactions with HEV are mediated in part by lymphocyte homing receptors and tissue-specific HEV determinants, the vascular addressins. A peripheral lymph node addressin (PNAd) has been detected immunohistologically in mouse and man by monoclonal antibody MECA-79, which inhibits lymphocyte homing to lymph nodes and lymphocyte binding to lymph node and tonsillar HEV. The human MECA-79 antigen, PNAd, is molecularly distinct from the 65-kD mucosal vascular addressin. The most abundant iodinated species by SDS-PAGE is 105 kD. When affinity isolated and immobilized on glass slides, MECA-79 immunoisolated material binds human and mouse lymphocytes avidly in a calcium dependent manner. Binding is blocked by mAb MECA-79, by antibodies against mouse or human LECAM-1 (the peripheral lymph node homing receptor, the MEL-14 antigen, LAM-1), and by treatment of PNAd with neuraminidase. Expression of LECAM-1 cDNA confers PNAd binding ability on a transfected B cell line. We conclude that LECAM-1 mediates lymphocyte binding to PNAd, an interaction that involves the lectin activity of LECAM-1 and carbohydrate determinants on the addressin.

scholarly journals Demonstration that a lectin-like receptor (gp90MEL) directly mediates adhesion of lymphocytes to high endothelial venules of lymph nodes.

1989 ◽  
Vol 109 (5) ◽  
pp. 2463-2469 ◽  
Author(s):  
J S Geoffroy ◽  
S D Rosen
Keyword(s):  
Lymph Node ◽  
Lymphoid Organ ◽  
Lymphoid Organs ◽  
Surface Glycoprotein ◽  
Lymphocyte Migration ◽  
Peripheral Lymph Node ◽  
Adhesive Interaction ◽  
High Endothelial Venules ◽  
Cell Surface Glycoprotein ◽  
Peripheral Lymph

Lymphocyte migration from the blood into most secondary lymphoid organs is initiated by a highly selective adhesive interaction with the endothelium of specialized blood vessels known as high endothelial venules (HEV). The propensity of lymphocytes to migrate to particular lymphoid organs is known as lymphocyte homing, and the receptors on lymphocytes that dictate interactions with HEV at particular anatomical sites are designated "homing receptors". Based upon antibody blockade experiments and cell-type distribution studies, a prominent candidate for the peripheral lymph node homing receptor in mouse is the approximately 90-kD cell surface glycoprotein (gp90MEL) recognized by the monoclonal antibody MEL-14. Previous work, including sequencing of a cDNA encoding for this molecule, supports the possibility that gp90MEL is a calcium-dependent lectin-like receptor. Here, we show that immunoaffinity-purified gp90MEL interacts in a sugar-inhibitable manner with sites on peripheral lymph node HEV and prevents attachment of lymphocytes. Lymphocyte attachment to HEV in Peyer's patches, a gut-associated lymphoid organ, is not affected by gp90MEL. The results demonstrate that gp90MEL, as a lectin-like receptor, directly bridges lymphocytes to the endothelium.

scholarly journals CC Chemokine Receptor 7–dependent and –independent Pathways for Lymphocyte Homing

2001 ◽  
Vol 194 (12) ◽  
pp. 1875-1881 ◽  
Author(s):  
Golo Henning ◽  
Lars Ohl ◽  
Tobias Junt ◽  
Phillip Reiterer ◽  
Volker Brinkmann ◽  
...  
Keyword(s):  
B Cells ◽  
Chemokine Receptor ◽  
Peripheral Blood ◽  
Lymphoid Tissues ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Peripheral Lymph ◽  
Independent Mechanism ◽  
Secondary Lymphoid Organs ◽  
Deficient Mice

Cognate interaction of chemokine receptor CCR7 on lymphocytes with its ligands CCL19 and CCL21 expressed on high endothelial venules (HEVs) is essential for effective migration of T and B cells across HEVs into secondary lymphoid organs. Plt mice, which lack expression of CCL19 and CCL21-ser, both ligands for CCR7 on HEVs, as well as CCR7-deficient mice, have a defective cell migration and reduced homing of lymphocytes. FTY720, a novel immunosuppressant, causes a reduction of lymphocytes in peripheral blood and tissues and their sequestration into lymphoid tissues. In this study we demonstrate that FTY720 rescues the homing defect in both CCR7−/− mice and plt mice. After FTY720 treatment, the number of CD4+ and CD8+ T cells as well as B cells in peripheral blood is reduced while pertussis toxin–sensitive homing into peripheral lymph nodes, mesenteric lymph node, and Peyer's patches is increased. Immunohistology demonstrates that FTY720 enables these cells to enter lymphoid tissue through HEVs. Thus, our data suggest an alternative G-αi-dependent, CCR7-CCL19/CCL21-independent mechanism for lymphocyte homing through HEVs which is strongly augmented in the presence of FTY720.

Orchidectomy and the immune response I. Effect of orchidectomy on lymphoid tissues of mice

1974 ◽  
Vol 185 (1081) ◽  
pp. 425-436 ◽  
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Lymphoid Tissues ◽  
Spleen Size ◽  
Thymic Involution ◽  
Peripheral Lymph Node ◽  
Peripheral Lymph ◽  
Lymph Node Enlargement ◽  
Spleen Mass ◽  
Lymph Node Mass

The effects of pre- and postpuberal orchidectomy on the lymphoid tissues of mice have been studied. Prepuberal orchidectomy delayed the normal rate of thymic involution and caused relative hypertrophy of the thymus which was maximal 1 month after surgery. There was also enlargement of the peripheral lymph nodes to reach a sustained maximum by 6 weeks and also an increase of spleen size. Histological examination of the enlarged thymus showed widening of the cortex and medulla with increased cell density. The enlarged peripheral lymph nodes showed widening of the paracortical area which is thymus dependent. Synchronous thymectomy and orchidectomy prevented the lymph node enlargement that follows orchidectomy alone, but it did not affect the increase of spleen size until 3 months after surgery. After postpuberal orchidectomy thymic size increased to a maximum at 1 month and the increase of peripheral lymph node mass and spleen mass was less than the changes following prepuberal surgery ; only 3 months after operation was the lymph node mass of orchidectomized mice significantly greater than controls and changes in spleen mass were only apparent after correction for changes in body mass.

scholarly journals Regulation of fucosyltransferase-VII expression in peripheral lymph node high endothelial venules

1998 ◽  
Vol 28 (10) ◽  
pp. 3040-3047 ◽  
Author(s):  
Vivette V. R. Swarte ◽  
David H. Joziasse ◽  
Dirk H. Van den Eijnden ◽  
Bronislawa Petryniak ◽  
John B. Lowe ◽  
...  
Keyword(s):  
Lymph Node ◽  
Peripheral Lymph Node ◽  
High Endothelial Venules ◽  
Peripheral Lymph

scholarly journals Requirement for sialic acid on the endothelial ligand of a lymphocyte homing receptor.

1990 ◽  
Vol 111 (6) ◽  
pp. 2757-2764 ◽  
Author(s):  
D D True ◽  
M S Singer ◽  
L A Lasky ◽  
S D Rosen
Keyword(s):  
Lymph Node ◽  
Sialic Acid ◽  
Critical Role ◽  
Lymphoid Organs ◽  
Lymphocyte Migration ◽  
Peripheral Lymph Node ◽  
Adhesive Interaction ◽  
High Endothelial Venules ◽  
Homing Receptor ◽  
Peripheral Lymph

The entry of blood-borne lymphocytes into most secondary lymphoid organs is initiated by a highly specific adhesive interaction with the specialized cuboidal endothelial cells of high endothelial venules (HEV). The adhesive receptors on lymphocytes that dictate interactions with HEV in different lymphoid organs are called homing receptors, signifying their critical role in controlling organ-selective lymphocyte migration. Considerable work has established that the mouse peripheral lymph node homing receptor (pnHR), defined by the mAb MEL-14, functions as a lectin-like adhesive protein. We have previously shown that sialidase treatment of peripheral lymph node (PN) HEV abrogates lymphocyte attachment to the HEV both in vivo and in vitro. We extend this evidence by demonstrating that Limax agglutinin (LA), a sialic acid-specific lectin, when reacted with HEV exposed in cryostat-cut tissue sections, blocks lymphocyte attachment to PN HEV and, unexpectedly, to the HEV of Peyer's patches (PP) as well. Using a recombinant form of the pnHR as a histochemical probe for its cognate adhesive site (HEV-ligand) on PN HEV, we demonstrate that both sialidase and Limax agglutinin functionally inactive this ligand. It is concluded that the requirement for sialic acid is at the level of the pnHR interaction with its HEV ligand. A distinct sialyloligosaccharide may encode the recognition determinant of a PP HEV ligand.

scholarly journals Homing receptors on human and rodent lymphocytes--evidence for a conserved carbohydrate-binding specificity

Blood ◽  
1987 ◽  
Vol 70 (6) ◽  
pp. 1842-1850
Author(s):  
LM Stoolman ◽  
TA Yednock ◽  
SD Rosen
Keyword(s):  
Functional Relationship ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Lymphoid Tissues ◽  
Carbohydrate Binding ◽  
Adhesive Interaction ◽  
High Endothelial Venules ◽  
Circulating Cells ◽  
Peripheral Lymph ◽  
The One

Lymphocyte recirculation begins with the attachment of circulating cells to the structurally distinctive postcapillary venules of lymphoid organs termed high-endothelial venules (HEVs). In both rodents and humans, the attachment of lymphocytes to the HEVs of peripheral lymph nodes (PNs) on the one hand and gut-associated lymphoid tissues (GALTs) on the other appears to involve discrete adhesive structures on the surfaces of the interacting cells. In rodents, we previously showed that a carbohydrate-binding receptor at the lymphocyte surface participates in the attachment to the HEV of peripheral nodes. The studies reported herein document the involvement of a similar receptor in the selective attachment of human peripheral blood lymphocytes to the HEVs of PNs. We argue that the close functional relationship between the human and rodent receptors indicates that this component of the adhesive interaction has been conserved through evolution.

scholarly journals Identification of a carbohydrate-based endothelial ligand for a lymphocyte homing receptor.

1991 ◽  
Vol 113 (5) ◽  
pp. 1213-1221 ◽  
Author(s):  
Y Imai ◽  
M S Singer ◽  
C Fennie ◽  
L A Lasky ◽  
S D Rosen
Keyword(s):  
Lymph Node ◽  
Peripheral Lymph Node ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Homing Receptor ◽  
Calcium Dependent ◽  
Lymph Node Homing ◽  
Recombinant Receptor ◽  
Peripheral Lymph ◽  
Mouse Lymphocytes

Lymphocyte attachment to high endothelial venules within lymph nodes is mediated by the peripheral lymph node homing receptor (pnHR), originally defined on mouse lymphocytes by the MEL-14 mAb. The pnHR is a calcium-dependent lectin-like receptor, a member of the LEC-CAM family of adhesion proteins. Here, using a soluble recombinant form of the homing receptor, we have identified an endothelial ligand for the pnHR as an approximately 50-kD sulfated, fucosylated, and sialylated glycoprotein, which we designate Sgp50 (sulfated glycoprotein of 50 kD). Recombinant receptor binding to this lymph node-specific glycoprotein requires calcium and is inhibitable by specific carbohydrates and by MEL-14 mAb. Sialylation of the component is required for binding. Additionally, the glycoprotein is precipitated by MECA-79, an adhesion-blocking mAb reactive with lymph node HEV. A related glycoprotein of approximately 90 kD (designated as Sgp90) is also identified.

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