Regulated expression of peripheral node addressin-positive high endothelial venules controls seeding of B lymphocytes into developing neonatal rabbit appendix

2006 ◽  
Vol 110 (1-2) ◽  
pp. 97-108 ◽  
Author(s):  
Rajesh K. Sinha ◽  
Cornelius Alexander ◽  
Rose G. Mage
Keyword(s):  
B Lymphocytes ◽  
High Endothelial Venules ◽  
Regulated Expression ◽  
Peripheral Node ◽  
Rabbit Appendix

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.

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 Essential role of peripheral node addressin in lymphocyte homing to nasal-associated lymphoid tissues and allergic immune responses

2011 ◽  
Vol 208 (5) ◽  
pp. 1015-1025 ◽  
Author(s):  
Yukari Ohmichi ◽  
Jotaro Hirakawa ◽  
Yasuyuki Imai ◽  
Minoru Fukuda ◽  
Hiroto Kawashima
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Specific Ige ◽  
Treg Cells ◽  
Lymphoid Tissues ◽  
Lymphocyte Homing ◽  
Double Knockout ◽  
High Endothelial Venules ◽  
Peripheral Node

Nasal-associated lymphoid tissue (NALT) is a mucosal immune tissue that provides immune responses against inhaled antigens. Lymphocyte homing to NALT is mediated by specific interactions between lymphocytes and high endothelial venules (HEVs) in NALT. In contrast to HEVs in other mucosal lymphoid tissues, NALT HEVs strongly express peripheral node addressins (PNAds) that bear sulfated glycans recognized by the monoclonal antibody MECA-79. We investigated the role of PNAd in lymphocyte homing to NALT using sulfotransferase N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST) 1 and GlcNAc6ST-2 double knockout (DKO) mice. The expression of PNAd in NALT HEVs was eliminated in DKO mice. Short-term homing assays indicated that lymphocyte homing to NALT was diminished by 90% in DKO mice. Production of antigen-specific IgE and the number of sneezes in response to nasally administered ovalbumin were also substantially diminished. Consistently, the NALT of DKO mice showed reduced production of IL-4 and increased production of IL-10 together with an increase in CD4+CD25+ regulatory T cells (Treg cells). Compared with the homing of CD4+CD25− conventional T cells, the homing of CD4+CD25+ Treg cells to NALT was less dependent on the L-selectin–PNAd interaction but was partially dependent on PSGL-1 (P-selectin glycoprotein ligand 1) and CD44. These results demonstrate that PNAd is essential for lymphocyte homing to NALT and nasal allergic responses.

scholarly journals Differentially regulated expression of 9-O-acetyl GD3 (CD60b) and 7-O-acetyl-GD3 (CD60c) during differentiation and maturation of human T and B lymphocytes

Glycobiology ◽  
2011 ◽  
Vol 21 (9) ◽  
pp. 1161-1172 ◽  
Author(s):  
D. Wipfler ◽  
G. V. Srinivasan ◽  
H. Sadick ◽  
B. Kniep ◽  
S. Arming ◽  
...  
Keyword(s):  
B Lymphocytes ◽  
T And B Lymphocytes ◽  
Regulated Expression

scholarly journals Nepmucin, a novel HEV sialomucin, mediates L-selectin–dependent lymphocyte rolling and promotes lymphocyte adhesion under flow

2006 ◽  
Vol 203 (6) ◽  
pp. 1603-1614 ◽  
Author(s):  
Eiji Umemoto ◽  
Toshiyuki Tanaka ◽  
Hidenobu Kanda ◽  
Soojung Jin ◽  
Kazuo Tohya ◽  
...  
Keyword(s):  
Microscopic Analysis ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Electron Microscopic ◽  
High Endothelial Venules ◽  
Lymphocyte Adhesion ◽  
Late Antigen ◽  
Ig Domain ◽  
Peripheral Node

Lymphocyte trafficking to lymph nodes (LNs) is initiated by the interaction between lymphocyte L-selectin and certain sialomucins, collectively termed peripheral node addressin (PNAd), carrying specific carbohydrates expressed by LN high endothelial venules (HEVs). Here, we identified a novel HEV-associated sialomucin, nepmucin (mucin not expressed in Peyer's patches [PPs]), that is expressed in LN HEVs but not detectable in PP HEVs at the protein level. Unlike conventional sialomucins, nepmucin contains a single V-type immunoglobulin (Ig) domain and a mucin-like domain. Using materials affinity-purified from LN lysates with soluble L-selectin, we found that two higher molecular weight species of nepmucin (75 and 95 kD) were decorated with oligosaccharides that bind L-selectin as well as an HEV-specific MECA-79 monoclonal antibody. Electron microscopic analysis showed that nepmucin accumulates in the extended luminal microvillus processes of LN HEVs. Upon appropriate glycosylation, nepmucin supported lymphocyte rolling via its mucin-like domain under physiological flow conditions. Furthermore, unlike most other sialomucins, nepmucin bound lymphocytes via its Ig domain, apparently independently of lymphocyte function–associated antigen 1 and very late antigen 4, and promoted shear-resistant lymphocyte binding in combination with intercellular adhesion molecule 1. Collectively, these results suggest that nepmucin may serve as a dual-functioning PNAd in LN HEVs, mediating both lymphocyte rolling and binding via different functional domains.

scholarly journals Ectopic LTαβ Directs Lymphoid Organ Neogenesis with Concomitant Expression of Peripheral Node Addressin and a HEV-restricted Sulfotransferase

2003 ◽  
Vol 197 (9) ◽  
pp. 1153-1163 ◽  
Author(s):  
Danielle L. Drayton ◽  
Xiaoyan Ying ◽  
Jason Lee ◽  
Werner Lesslauer ◽  
Nancy H. Ruddle
Keyword(s):  
B Cell ◽  
Cell Adhesion Molecule ◽  
Lymphoid Organ ◽  
Wild Type ◽  
High Endothelial Venules ◽  
Insulin Promoter ◽  
Cell Compartmentalization ◽  
Antigen Presenting ◽  
Lymphoid Organogenesis ◽  
Peripheral Node

Lymph node (LN) function depends on T and B cell compartmentalization, antigen presenting cells, and high endothelial venules (HEVs) expressing mucosal addressin cell adhesion molecule (MAdCAM-1) and peripheral node addressin (PNAd), ligands for naive cell entrance into LNs. Luminal PNAd expression requires a HEV-restricted sulfotransferase (HEC-6ST). To investigate LTαβ's activities in lymphoid organogenesis, mice simultaneously expressing LTα and LTβ under rat insulin promoter II (RIP) control were compared with RIPLTα mice in a model of lymphoid neogenesis and with LTβ−/− mice. RIPLTαβ pancreata exhibited massive intra-islet mononuclear infiltrates that differed from the more sparse peri-islet cell accumulations in RIPLTα pancreata: separation into T and B cell areas was more distinct with prominent FDC networks, expression of lymphoid chemokines (CCL21, CCL19, and CXCL13) was more intense, and L-selectin+ cells were more frequent. In contrast to the predominant abluminal PNAd pattern of HEV in LTβ−/− MLN and RIPLTα pancreatic infiltrates, PNAd was expressed at the luminal and abluminal aspects of HEV in wild-type LN and in RIPLTαβ pancreata, coincident with HEC-6ST. These data highlight distinct roles of LTα and LTαβ in lymphoid organogenesis supporting the notion that HEC-6ST–dependent luminal PNAd is under regulation by LTαβ.

scholarly journals Neutrophils recruited through high endothelial venules of the lymph nodes via PNAd intercept disseminating Staphylococcus aureus

2018 ◽  
Vol 115 (10) ◽  
pp. 2449-2454 ◽  
Author(s):  
Ania Bogoslowski ◽  
Eugene C. Butcher ◽  
Paul Kubes
Keyword(s):  
Staphylococcus Aureus ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Systemic Circulation ◽  
Skin Infections ◽  
High Endothelial Venules ◽  
Novel Treatments ◽  
Subcapsular Sinus ◽  
Draining Lymph Node ◽  
Peripheral Node

Staphylococcus aureus is a skin- and respiratory tract-colonizing bacterium and is the leading cause of community-acquired skin infections. Dissemination of these bacteria into systemic circulation causes bacteremia, which has a high mortality rate. Therefore, understanding the immunologic barriers that prevent dissemination is critical to developing novel treatments. In this study, we demonstrate that an S. aureus breach across skin leads to some migration of the pathogen to the draining lymph node, but no further. While subcapsular sinus (SCS) macrophage in lymph nodes were important in detaining S. aureus, a rapid complement-dependent neutrophil recruitment (independent of the SCS macrophage) via high endothelial venules (HEVs) resulted in high numbers of neutrophils that intercepted the bacteria in the lymph nodes. Peripheral Node Addressin together with its two ligands, L-selectin and platelet P-selectin, are critical for recruiting neutrophils via the HEVs. Almost no neutrophils entered the lymph nodes via lymphatics. Neutrophils actively phagocytosed S. aureus and helped sterilize the lymph nodes and prevent dissemination to blood and other organs.

scholarly journals Helicobacter-Induced Chronic Active Lymphoid Aggregates Have Characteristics of Tertiary Lymphoid Tissue

2003 ◽  
Vol 71 (6) ◽  
pp. 3572-3577 ◽  
Author(s):  
Nirah H. Shomer ◽  
James G. Fox ◽  
Amy E. Juedes ◽  
Nancy H. Ruddle
Keyword(s):  
Chronic Active Hepatitis ◽  
Lymphoid Organ ◽  
Lymphoid Organs ◽  
High Endothelial Venules ◽  
Inflammatory Lesions ◽  
Tissue Sections ◽  
Inflammatory Infiltrates ◽  
Lymphoid Aggregates ◽  
Peripheral Node

ABSTRACT Susceptible strains of mice that are naturally or experimentally infected with murine intestinal helicobacter species develop hepatic inflammatory lesions that have previously been described as chronic active hepatitis. The inflammatory infiltrates in some models of chronic autoimmunity or inflammation resemble tertiary lymphoid organs hypothesized to arise by a process termed lymphoid organ neogenesis. To determine whether hepatic inflammation caused by infection with helicobacter could give rise to tertiary lymphoid organs, we used fluorescence-activated cell sorting, immunohistochemistry, and in situ hybridization techniques to identify specific components characteristic of lymphoid organs in liver tissue sections and liver cell suspensions from helicobacter-infected mice. Small venules (high endothelial venules [HEVs]) in inflammatory lesions in Helicobacter species-infected livers were positive for peripheral node addressin. Mucosal addressin cell adhesion molecule also stained HEVs and cells with a staining pattern consistent with scattered stromal cells. The chemokines SLC (CCL 21) and BLC (CXCL13) were present, as were B220-positive B cells and T cells. The latter included a naïve (CD45lo-CD62Lhi) population. These findings suggest that helicobacter-induced chronic active hepatitis arises through the process of lymphoid organ neogenesis.

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.

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