N-acetylglucosamine-6-O-sulfotransferases 1 and 2 cooperatively control lymphocyte homing through L-selectin ligand biosynthesis in high endothelial venules

2005 ◽  
Vol 6 (11) ◽  
pp. 1096-1104 ◽  
Author(s):  
Hiroto Kawashima ◽  
Bronislawa Petryniak ◽  
Nobuyoshi Hiraoka ◽  
Junya Mitoma ◽  
Valerie Huckaby ◽  
...  
Keyword(s):  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Selectin Ligand

scholarly journals Sialomucin CD34 is the major L-selectin ligand in human tonsil high endothelial venules.

1995 ◽  
Vol 131 (1) ◽  
pp. 261-270 ◽  
Author(s):  
K D Puri ◽  
E B Finger ◽  
G Gaudernack ◽  
T A Springer
Keyword(s):  
Complex Mixture ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Human Tonsil ◽  
Hematopoietic Cell Line ◽  
Selectin Ligands ◽  
Selectin Ligand ◽  
Peripheral Node ◽  
Ligand Activity

Peripheral node addressin (PNAd) is a complex mixture of glycoproteins with L-selectin ligand activity that functions in lymphocyte homing. We have investigated the contribution of the sialomucin CD34 relative to other components of PNAd in lymphocyte tethering and rolling in in vitro laminar flow assays. PNAd was isolated with MECA-79 mAb-Sepharose from tonsillar stroma, and the CD34 component (PNAd,CD34+) and CD34-negative component (PNAd,CD34-) separated on CD34 mAb-Sepharose. Lymphocytes on the PNAd,CD34- fraction tether less efficiently, roll faster and are less resistant to shear detachment than on PNAd. The PNAd,CD34+ fraction constitutes about half the total functional activity. These studies show that CD34 is a major functional component of PNAd. Ligand activity in both the PNAd,CD34+ and PNAd,CD34- fractions is expressed on mucin-like domains, as shown with O-sialoglycoprotease. The CD34 component of PNAd has about four times higher tethering efficiency than total tonsillar CD34. CD34 from spleen shows no lymphocyte tethering. Although less efficient than the PNAd,CD34+ fraction from tonsil, CD34 from the KG1a hematopoietic cell line is functionally active as an L-selectin ligand despite lack of reactivity with MECA-79 mAb, which binds to a sulfation-dependent epitope. All four forms of CD34 are active in binding to E-selectin. KG1a CD34 but not spleen CD34 are active as L-selectin ligands, yet both lack MECA-79 reactivity and possess E-selectin ligand activity. This suggests that L-selectin ligands and E-selectin ligands differ in more respects than presence of the MECA-79 epitope.

Sulphated endothelial ligands for L-selectin in lymphocyte homing and inflammation

2003 ◽  
Vol 31 (2) ◽  
pp. 313-317 ◽  
Author(s):  
A. van Zante ◽  
S.D. Rosen
Keyword(s):  
Monoclonal Antibody ◽  
Endothelial Cells ◽  
Lymphoid Tissues ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Selectin Ligands ◽  
Peripheral Lymph ◽  
Selectin Ligand ◽  
Endothelial Ligands ◽  
Peripheral Node

Lymphocytes from the blood home to secondary lymphoid tissues through a process of tethering, rolling, firm adhesion and transmigration. Tethering and rolling of lymphocytes is mediated by the interaction of L-selectin on lymphocytes with sulphated ligands expressed by the specialized endothelial cells of high endothelial venules (HEVs). The sulphate-dependent monoclonal antibody MECA79 stains HEVs in peripheral lymph nodes and recognizes the complex of HEV ligands for L-selectin termed peripheral node addressin. High endothelial cell GlcNAc-6-sulphotransferase/L-selectin ligand sulphotransferase is a HEV-expressed sulphotransferase that contributes to the formation of the MECA79 epitope and L-selectin ligands on lymph node HEVs. MECA79-reactive vessels are also common at sites of chronic inflammation, suggesting mechanistic parallels between lymphocyte homing and inflammatory trafficking.

Sulfated Sialyl Lewis X, the Putative L-Selectin Ligand, Detected on Endothelial Cells of High Endothelial Venules by a Distinct Set of Anti-Sialyl Lewis X Antibodies

1997 ◽  
Vol 230 (3) ◽  
pp. 546-551 ◽  
Author(s):  
Chikako Mitsuoka ◽  
Naoko Kawakami-Kimura ◽  
Mikiko Kasugai-Sawada ◽  
Nozomu Hiraiwa ◽  
Ken'ichi Toda ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Sialyl Lewis X ◽  
Lewis X ◽  
High Endothelial Venules ◽  
Sialyl Lewis ◽  
Selectin Ligand

scholarly journals Lymphocyte Homing to Bronchus-associated Lymphoid Tissue (BALT) Is Mediated by L-selectin/PNAd, α4β1 Integrin/VCAM-1, and LFA-1 Adhesion Pathways

2003 ◽  
Vol 197 (10) ◽  
pp. 1255-1267 ◽  
Author(s):  
Baohui Xu ◽  
Norbert Wagner ◽  
Linh Nguyen Pham ◽  
Vincent Magno ◽  
Zhongyan Shan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Lymphoid Tissue ◽  
Lymphoid Tissues ◽  
Lymphocyte Migration ◽  
High Endothelial Venules ◽  
Level Of Involvement ◽  
Selectin Ligand ◽  
High Level ◽  
Migration Pathways ◽  
B And T Lymphocytes

Bronchus-associated lymphoid tissue (BALT) participates in airway immune responses. However, little is known about the lymphocyte–endothelial adhesion cascades that recruit lymphocytes from blood into BALT. We show that high endothelial venules (HEVs) in BALT express substantial levels of VCAM-1, in marked contrast to HEVs in other secondary lymphoid tissues. BALT HEVs also express the L-selectin ligand PNAd. Anti–L-selectin, anti-PNAd, and anti–LFA-1 mAbs almost completely block the homing of B and T lymphocytes into BALT, whereas anti–α4 integrin and anti–VCAM-1 mAbs inhibit homing by nearly 40%. α4β7 integrin and MAdCAM-1 are not involved. Importantly, we found that mAbs against α4 integrin and VCAM-1 significantly block the migration of total T cells (80% memory phenotype) but not naive T and B cells to BALT. These results suggest that an adhesion cascade, which includes L-selectin/PNAd, α4β1 integrin/VCAM-1, and LFA-1, targets specific lymphocyte subsets to BALT. This high level of involvement of α4β1 integrin/VCAM-1 is unique among secondary lymphoid tissues, and may help unify lymphocyte migration pathways and immune responses in BALT and other bronchopulmonary tissues.

Core 2 branching β1,6-N-acetylglucosaminyltransferase and high endothelial cell N-acetylglucosamine-6-sulfotransferase exert differential control over B- and T-lymphocyte homing to peripheral lymph nodes

Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 4104-4112 ◽  
Author(s):  
Jean-Marc Gauguet ◽  
Steven D. Rosen ◽  
Jamey D. Marth ◽  
Ulrich H. von Andrian
Keyword(s):  
T Cells ◽  
Endothelial Cell ◽  
T Cell ◽  
B Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Rolling Velocity ◽  
Peripheral Lymph

Abstract Blood-borne lymphocyte trafficking to peripheral lymph nodes (PLNs) depends on the successful initiation of rolling interactions mediated by L-selectin binding to sialomucin ligands in high endothelial venules (HEVs). Biochemical analysis of purified L-selectin ligands has identified posttranslational modifications mediated by Core2GlcNAcT-I and high endothelial cell GlcNAc-6-sulfotransferase (HECGlcNAc6ST). Consequently, lymphocyte migration to PLNs of C2GlcNAcT-I-/- and HEC-GlcNAc6ST-/- mice was reduced; however, B-cell homing was more severely compromised than T-cell migration. Accordingly, intravital microscopy (IVM) of PLN HEVs revealed a defect in B-cell tethering and increased rolling velocity (Vroll) in C2GlcNAcT-I-/- mice that was more pronounced than it was for T cells. By contrast, B- and T-cell tethering was normal in HEC-GlcNAc6ST-/- HEVs, but Vroll was accelerated, especially for B cells. The increased sensitivity of B cells to glycan deficiencies was caused by lower expression levels of L-selectin; L-selectin+/- T cells expressing L-selectin levels equivalent to those of B cells exhibited intravascular behavior similar to that of B cells. These results demonstrate distinct functions for C2GlcNAcT-I and HEC-GlcNAc6ST in the differential elaboration of HEV glycoproteins that set a threshold for the amount of L-selectin needed for lymphocyte homing. (Blood. 2004;104:4104-4112)

scholarly journals Fucoidin, but not yeast polyphosphomannan PPME, inhibits leukocyte rolling in venules of the rat mesentery

Blood ◽  
1993 ◽  
Vol 81 (1) ◽  
pp. 177-185 ◽  
Author(s):  
K Ley ◽  
G Linnemann ◽  
M Meinen ◽  
LM Stoolman ◽  
P Gaehtgens
Keyword(s):  
Leukocyte Adhesion ◽  
Sulfated Polysaccharides ◽  
Leukocyte Rolling ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Lymphocyte Adhesion ◽  
Adhesion Receptor ◽  
Rat Mesentery ◽  
Rolling Leukocytes ◽  
Rolling Leukocyte

Abstract Leukocyte rolling in venules is inhibited by several sulfated polysaccharides, by antibodies to the leukocyte adhesion receptor L- selectin (LECAM-1), and by recombinant soluble L-selectin. The sulfated fucose polymer fucoidin and the polyphosphomannan PPME bind to L- selectin and inhibit L-selectin-mediated lymphocyte adhesion to lymph node high endothelial venules (LN-HEV). We investigated whether fucoidin and PPME also inhibit leukocyte rolling. Rolling leukocyte flux was determined by intravital microscopy in 47 venules (diameter 21 to 50 microns) of the rat mesentery with and without micro-infusion of each reagent through 8-microns glass micropipettes. Micro-infusion (1 mg/mL) or intravenous (IV) injection (25 mg/kg) of fucoidin, but not vehicle, reduced leukocyte rolling by greater than 90%. The half- effective concentration was approximately 2.5 micrograms/mL. Stroboscopic fluorescence video microscopy showed that fucoidin decreased the fraction of rolling leukocytes from 44% of all leukocytes passing the venules in control to less than 1%. PPME micro-infusion (1 mg/mL) or IV injection (14 mg/kg) did not reduce leukocyte rolling. Hence, leukocyte rolling differs from lymphocyte homing with respect to the effect of PPME. This may be related to fucoidin binding to L- selectin with greater affinity than PPME. Alternatively, inflamed venular endothelium may express a ligand for L-selectin different from that constitutively expressed on LN-HEV.

Human Conjunctiva Contains High Endothelial Venules That Express Lymphocyte Homing Receptors

1999 ◽  
Vol 69 (4) ◽  
pp. 397-403 ◽  
Author(s):  
RICHARD JOHN HAYNES ◽  
PATRICK JASON TIGHE ◽  
ROBERT ALASTAIR HOWIE SCOTT ◽  
HARMINDER SINGH DUA
Keyword(s):  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Lymphocyte Homing Receptors ◽  
Human Conjunctiva

scholarly journals A Novel Endothelial L-Selectin Ligand Activity in Lymph Node Medulla That Is Regulated by α(1,3)-Fucosyltransferase-IV

2003 ◽  
Vol 198 (9) ◽  
pp. 1301-1312 ◽  
Author(s):  
Christine M'Rini ◽  
Guiying Cheng ◽  
Colleen Schweitzer ◽  
Lois L. Cavanagh ◽  
Roger T. Palframan ◽  
...  
Keyword(s):  
Mrna Level ◽  
Surrogate Marker ◽  
High Endothelial Venules ◽  
Cell Homing ◽  
Selectin Ligands ◽  
Peripheral Lymph ◽  
T Cell Homing ◽  
Selectin Ligand ◽  
Peripheral Node ◽  
Ligand Activity

Lymphocytes home to peripheral lymph nodes (PLNs) via high endothelial venules (HEVs) in the subcortex and incrementally larger collecting venules in the medulla. HEVs express ligands for L-selectin, which mediates lymphocyte rolling. L-selectin counterreceptors in HEVs are recognized by mAb MECA-79, a surrogate marker for molecularly heterogeneous glycans termed peripheral node addressin. By contrast, we find that medullary venules express L-selectin ligands not recognized by MECA-79. Both L-selectin ligands must be fucosylated by α(1,3)-fucosyltransferase (FucT)-IV or FucT-VII as rolling is absent in FucT-IV+VII−/− mice. Intravital microscopy experiments revealed that MECA-79–reactive ligands depend primarily on FucT-VII, whereas MECA-79–independent medullary L-selectin ligands are regulated by FucT-IV. Expression levels of both enzymes paralleled these anatomical distinctions. The relative mRNA level of FucT-IV was higher in medullary venules than in HEVs, whereas FucT-VII was most prominent in HEVs and weak in medullary venules. Thus, two distinct L-selectin ligands are segmentally confined to contiguous microvascular domains in PLNs. Although MECA-79–reactive species predominate in HEVs, medullary venules express another ligand that is spatially, antigenically, and biosynthetically unique. Physiologic relevance for this novel activity in medullary microvessels is suggested by the finding that L-selectin–dependent T cell homing to PLNs was partly insensitive to MECA-79 inhibition.

scholarly journals Identification of a Major Carbohydrate Capping Group of the L-selectin Ligand on High Endothelial Venules in Human Lymph Nodes as 6-Sulfo Sialyl Lewis X

1998 ◽  
Vol 273 (18) ◽  
pp. 11225-11233 ◽  
Author(s):  
Chikako Mitsuoka ◽  
Mikiko Sawada-Kasugai ◽  
Keiko Ando-Furui ◽  
Mineko Izawa ◽  
Hayao Nakanishi ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Sialyl Lewis X ◽  
Lewis X ◽  
High Endothelial Venules ◽  
Sialyl Lewis ◽  
Selectin Ligand

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.

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