scholarly journals Identification of Podocalyxin-like Protein as a High Endothelial Venule Ligand for L-selectin: Parallels to CD34

1998 ◽  
Vol 187 (12) ◽  
pp. 1965-1975 ◽  
Author(s):  
Christopher Sassetti ◽  
Kirsten Tangemann ◽  
Mark S. Singer ◽  
David B. Kershaw ◽  
Steven D. Rosen
Keyword(s):  
Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Structural Features ◽  
High Endothelial Venules ◽  
Lectin Domain ◽  
Kidney Glomerulus ◽  
Selectin Ligand ◽  
Definition Of ◽  
Secondary Lymphoid Organs

The leukocyte adhesion molecule, L-selectin, mediates the recruitment of lymphocytes to secondary lymphoid organs via interactions with specific ligands presented on high endothelial venules (HEV). Although the HEV-derived ligands for L-selectin are still incompletely defined, they share a common sialomucin-like structure which is thought to present clustered oligosaccharides to the lectin domain of L-selectin. Podocalyxin-like protein (PCLP) is a transmembrane sialomucin that is similar in structure to the well-characterized L-selectin ligand CD34. PCLP has been shown previously to be expressed on the foot processes of podocytes in the kidney glomerulus as well as on vascular endothelium at some sites. We have determined that PCLP is present on HEV, where it binds to both recombinant L-selectin and the HEV-specific monoclonal antibody MECA-79. Furthermore, purified HEV-derived PCLP is able to support the tethering and rolling of lymphocytes under physiological flow conditions in vitro. These results suggest a novel function for PCLP as an adhesion molecule and allow the definition of conserved structural features in PCLP and CD34, which may be important for L-selectin ligand function.

scholarly journals The three members of the selectin receptor family recognize a common carbohydrate epitope, the sialyl Lewis(x) oligosaccharide

1992 ◽  
Vol 117 (4) ◽  
pp. 895-902 ◽  
Author(s):  
C Foxall ◽  
SR Watson ◽  
D Dowbenko ◽  
C Fennie ◽  
LA Lasky ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Structural Features ◽  
Sialyl Lewis X ◽  
Lewis X ◽  
Leukocyte Adhesion Molecule ◽  
Lectin Domain ◽  
Calcium Dependent ◽  
Carbohydrate Epitope ◽  
Sialyl Lewis

The selectins (lectin-EGF-complement binding-cell adhesion molecules [LEC-CAMs]) are a family of mammalian receptors implicated in the initial interactions between leukocytes and vascular endothelia, leading to lymphocyte homing, platelet binding, and neutrophil extravasation. The three known selectins, L-selectin (leukocyte adhesion molecule-1 [LECAM-1]), E-selectin (endothelial-leukocyte adhesion molecule-1 [ELAM-1]), and P-selectin (GMP-140) share structural features that include a calcium-dependent lectin domain. The sialyl Lewis(x) carbohydrate epitope has been reported as a ligand for both E- and P-selectins. Although L-selectin has been demonstrated to bind to carbohydrates, structural features of potential mammalian carbohydrate ligand(s) have not been well defined. Using an ELISA developed with a sialyl Lewis(x)-containing glycolipid and an E-selectin-IgG chimera, we have demonstrated the direct binding of the L-selectin-IgG chimera to sialyl Lewis(x). This recognition was calcium dependent, and could be blocked by Mel-14 antibody but not by other antibodies. Recognition was confirmed by the ability of cells expressing the native L-selectin to adhere to immobilized sialyl Lewis(x). These data suggest that the sialyl Lewis(x) oligosaccharide may form the basis of a recognition domain common to all three selectins.

scholarly journals Molecules and structures involved in the adhesion of natural killer cells to vascular endothelium.

1991 ◽  
Vol 173 (2) ◽  
pp. 439-448 ◽  
Author(s):  
P Allavena ◽  
C Paganin ◽  
I Martin-Padura ◽  
G Peri ◽  
M Gaboli ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Adhesion Molecule ◽  
Vascular Endothelium ◽  
Nk Cell ◽  
Leukocyte Adhesion ◽  
Umbilical Vein ◽  
Interleukin 2 ◽  
Intercellular Adhesion Molecule

The present study was designed to define molecules and structures involved in the interaction of natural killer (NK) cells with the vascular endothelium in vitro. Resting and interleukin 2 (IL-2)-activated NK cells were studied for their capacity to adhere to resting and IL-1-treated human umbilical vein endothelial cells (EC). In the absence of stimuli, NK cells showed appreciable adhesion to EC, with levels of binding intermediate between polymorphs and monocytes. The binding ability was increased by pretreatment of NK cells with IL-2. Using the appropriate monoclonal antibody, the beta 2 leukocyte integrin CD18/CD11a was identified as the major adhesion pathway of NK cells to unstimulated EC. Activation of EC with IL-1 increased the binding of NK cells. In addition to the CD18-CD11a/intercellular adhesion molecule pathway, the interaction of resting or IL-2-activated NK cells to IL-1-activated EC involved the VLA-4 (alpha 4 beta 1)-vascular cell adhesion molecule 1 receptor/counter-receptor pair. No evidence for appreciable involvement of endothelial-leukocyte adhesion molecule was obtained. Often, NK cells interacted either with the culture substrate or with the EC surface via dot-shaped adhesion structures (podosomes) protruding from the ventral surface and consisting of a core of F-actin surrounded by a ring of vinculin and talin. The identification of molecules and microanatomical structures involved in the interaction of NK cells with EC may provide a better understanding of the regulation of NK cell recruitment from blood, their extravasation, and their migration to tissues.

Characterization of Plasmodium falciparum-Infected Erythrocyte and P-Selectin Interaction Under Flow Conditions

Blood ◽  
1998 ◽  
Vol 91 (12) ◽  
pp. 4803-4809 ◽  
Author(s):  
May Ho ◽  
Tineke Schollaardt ◽  
Xiaofei Niu ◽  
Sornchai Looareesuwan ◽  
Kamala D. Patel ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Adhesion Molecule ◽  
Sialic Acid Residue ◽  
Intercellular Adhesion Molecule ◽  
Flow Conditions ◽  
Intercellular Adhesion Molecule 1 ◽  
Adhesive Interaction ◽  
Lectin Domain

Abstract Plasmodium falciparum-infected erythrocytes (IRBC) roll on the adhesion molecule P-selectin in vitro under flow conditions that approximate the shear stress in capillary and postcapillary venules in which cytoadherence occurs in vivo. The pathological significance of this adhesive interaction is currently unknown. In this study, we further investigated the molecular interactions between IRBC and P-selectin by using a laminar flow system that allowed for the direct visualization of IRBC-substratum interactions. The results showed that the IRBC–P-selectin interaction was Ca2+-dependent and involved the lectin domain of P-selectin and a sialic acid residue on IRBC. The sialylated P-selectin ligand was trypsin-sensitive, which suggests that it could be part of the parasite antigen PfEMP1 that interacts with CD36 and intercellular adhesion molecule-1 (ICAM-1), but different from a trypsin-resistant IRBC ligand that adheres selectively to chondroitin sulfate A. Studies on the rolling and adhesion of IRBC on activated platelets that express both CD36 and P-selectin showed that inhibition of rolling on P-selectin reduced the adhesion of some clinical parasite isolates to CD36, whereas other parasite isolates appeared to interact directly with CD36. Thus, cytoadherence under physiological flow conditions may be mediated by multiple IRBC ligands that interact with different adhesion molecules in a cooperative fashion. These findings underscore the complexity of the interactions betweeen IRBC and vascular endothelium.

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 An inflammation-induced mechanism for leukocyte transmigration across lymphatic vessel endothelium

2006 ◽  
Vol 203 (12) ◽  
pp. 2763-2777 ◽  
Author(s):  
Louise A. Johnson ◽  
Steven Clasper ◽  
Andrew P. Holt ◽  
Patricia F. Lalor ◽  
Dilair Baban ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Lymphatic Vessels ◽  
Contact Hypersensitivity ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Leukocyte Transmigration ◽  
Antiinflammatory Therapy ◽  
Skin Contact

The exit of antigen-presenting cells and lymphocytes from inflamed skin to afferent lymph is vital for the initiation and maintenance of dermal immune responses. How such an exit is achieved and how cells transmigrate the distinct endothelium of lymphatic vessels are unknown. We show that inflammatory cytokines trigger activation of dermal lymphatic endothelial cells (LECs), leading to expression of the key leukocyte adhesion receptors intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin, as well as a discrete panel of chemokines and other potential regulators of leukocyte transmigration. Furthermore, we show that both ICAM-1 and VCAM-1 are induced in the dermal lymphatic vessels of mice exposed to skin contact hypersensitivity where they mediate lymph node trafficking of dendritic cells (DCs) via afferent lymphatics. Lastly, we show that tumor necrosis factor α stimulates both DC adhesion and transmigration of dermal LEC monolayers in vitro and that the process is efficiently inhibited by ICAM-1 and VCAM-1 adhesion-blocking monoclonal antibodies. These results reveal a CAM-mediated mechanism for recruiting leukocytes to the lymph nodes in inflammation and highlight the process of lymphatic transmigration as a potential new target for antiinflammatory therapy.

scholarly journals Monocyte attachment to activated human vascular endothelium in vitro is mediated by leukocyte adhesion molecule-1 (L-selectin) under nonstatic conditions.

1992 ◽  
Vol 175 (6) ◽  
pp. 1789-1792 ◽  
Author(s):  
O Spertini ◽  
F W Luscinskas ◽  
M A Gimbrone ◽  
T F Tedder
Keyword(s):  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Cell Attachment ◽  
Leukocyte Adhesion ◽  
Vascular Cell Adhesion ◽  
Leukocyte Adhesion Molecule ◽  
Endothelial Monolayers ◽  
Endothelial Leukocyte Adhesion Molecule ◽  
Cell Adhesion Molecule 1

The receptors that mediate monocyte adhesion to cytokine-stimulated endothelial monolayers were assessed using a nonstatic (rotating) cell-attachment assay. In this system, leukocyte adhesion molecule-1 (LAM-1) (L-selectin) mediated a major portion (87 +/- 15% at 37 degrees C) of monocyte attachment to activated endothelium. mAb blocking of endothelial leukocyte adhesion molecule-1 (41% inhibition), CD18 (36%), and vascular cell adhesion molecule-1 (25%) function had lesser effects on attachment. These results suggest that LAM-1 may serve an important role in monocyte attachment to endothelium at sites of inflammation.

scholarly journals Non-Canonical G-quadruplexes cause the hCEB1 minisatellite instability in Saccharomyces cerevisiae

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Aurèle Piazza ◽  
Xiaojie Cui ◽  
Michael Adrian ◽  
Frédéric Samazan ◽  
Brahim Heddi ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Structure Function ◽  
Genomic Instability ◽  
Function Analysis ◽  
Structural Features ◽  
Detectable Effect ◽  
Definition Of ◽  
And Function

G-quadruplexes (G4) are polymorphic four-stranded structures formed by certain G-rich nucleic acids in vitro, but the sequence and structural features dictating their formation and function in vivo remains uncertain. Here we report a structure-function analysis of the complex hCEB1 G4-forming sequence. We isolated four G4 conformations in vitro, all of which bear unusual structural features: Form 1 bears a V-shaped loop and a snapback guanine; Form 2 contains a terminal G-triad; Form 3 bears a zero-nucleotide loop; and Form 4 is a zero-nucleotide loop monomer or an interlocked dimer. In vivo, Form 1 and Form 2 differently account for 2/3rd of the genomic instability of hCEB1 in two G4-stabilizing conditions. Form 3 and an unidentified form contribute to the remaining instability, while Form 4 has no detectable effect. This work underscores the structural polymorphisms originated from a single highly G-rich sequence and demonstrates the existence of non-canonical G4s in cells, thus broadening the definition of G4-forming sequences.

CXCL13 is an arrest chemokine for B cells in high endothelial venules

Blood ◽  
2005 ◽  
Vol 106 (8) ◽  
pp. 2613-2618 ◽  
Author(s):  
Naotoshi Kanemitsu ◽  
Yukihiko Ebisuno ◽  
Toshiyuki Tanaka ◽  
Kazuhiro Otani ◽  
Haruko Hayasaka ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
B Cells ◽  
B Cell ◽  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
High Endothelial Venules ◽  
Guanosine Triphosphatase ◽  
Cell Adhesion Molecule 1

Abstract Chemokine receptor signaling is critical for lymphocyte trafficking across high endothelial venules (HEVs), but the exact mode of action of individual chemokines expressed in the HEVs is unclear. Here we report that CXCL13, expressed in a substantial proportion of HEVs in both lymph nodes (LNs) and Peyer patches (PPs), serves as an arrest chemokine for B cells. Whole-mount analysis of mesenteric LNs (MLNs) showed that, unlike T cells, B cellsa dhere poorly to the HEVs of CXCL13–/– mice and that B-cell adhesion is substantially restored in CXCL13–/– HEVs when CXCL13 is added to the MLNs by superfusion, as we have previously observed in PP HEVs by intravital microscopy. In vitro, CXCL13 activated the small guanosine triphosphatase (GTPase) Rap1 in B cells, and corroborating this observation, a deficiency of RAPL, the Rap1 effector molecule, caused a significant reduction in shear-resistant B-cell adhesion to intercellular adhesion molecule 1 (ICAM-1). In addition, CXCL13 induced B-cell adhesion to mucosal addressin cell adhesion molecule 1 (MAdCAM-1) by activating α4 integrin. These data identify CXCL13 as an arrest chemokine for B cells in HEVs and show that CXCL13 plays an important role in B-cell entry into not only PPs but also MLNs.

scholarly journals Antibodies against human neutrophil LECAM-1 (LAM-1/Leu-8/DREG-56 antigen) and endothelial cell ELAM-1 inhibit a common CD18-independent adhesion pathway in vitro

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 805-811 ◽  
Author(s):  
TK Kishimoto ◽  
RA Warnock ◽  
MA Jutila ◽  
EC Butcher ◽  
C Lane ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Neutrophil Function ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1

Neutrophil adhesion to interleukin-1 (IL-1)-stimulated human umbilical vein endothelial cells (HUVEC) involves the CD18 family of leukocyte integrins (lymphocyte function-associated antigen-1 [LFA-1], Mac-1, and p150,95) and LECAM-1 (DREG-56/LEU-8/LAM-1 antigen) on neutrophils and intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1) on the endothelium. In this study, we compare CD18-independent adhesion pathways mediated by neutrophil LECAM- 1 and endothelial ELAM-1 and find that these two pathways overlap in a variety of assays: (1) anti-LECAM-1 and anti-ELAM-1 monoclonal antibody (MoAb) inhibit neutrophil binding to HUVEC, and the inhibitory effect is not additive; (2) anti-LECAM-1 MoAb, like anti-ELAM-1 MoAb, inhibits neutrophil binding to HUVEC stimulated for 3 hours with IL-1, but not to HUVEC stimulated for 8 hours, by which time ELAM-1 expression is downregulated; (3) anti-ELAM-1 MoAb has no effect on transendothelial migration, a CD18-dependent, LECAM-1-independent neutrophil function. Interestingly, anti-ELAM MoAb has a reduced but significant inhibitory effect on the adhesion of activated neutrophils that have shed their cell-surface LECAM-1. We also show that neutrophil binding to ELAM-1- transfected L cells is inhibited not only by anti-ELAM-1 but also by anti-LECAM-1 MoAb. These results suggest that LECAM-1 and ELAM-1 can operate in the same adhesion pathway, possibly as a receptor- counterreceptor pair. LECAM-1 and ELAM-1 are likely to interact with other ligands as well, perhaps through carbohydrate determinants that modify more than one glycoprotein.

scholarly journals Regulation of leukocyte rolling and adhesion to high endothelial venules through the cytoplasmic domain of L-selectin.

1993 ◽  
Vol 177 (3) ◽  
pp. 833-838 ◽  
Author(s):  
G S Kansas ◽  
K Ley ◽  
J M Munro ◽  
T F Tedder
Keyword(s):  
Amino Acid ◽  
Leukocyte Adhesion ◽  
Frozen Section ◽  
Cytoplasmic Domain ◽  
Leukocyte Rolling ◽  
High Endothelial Venules ◽  
Peripheral Lymph ◽  
Selectin Family

L-selectin (leukocyte adhesion molecule 1/MEL-14), a member of the selectin family of cell adhesion molecules, mediates leukocyte rolling and leukocyte adhesion to endothelium at sites of inflammation. In addition, L-selectin mediates the binding of lymphocytes to high endothelial venules (HEV) of peripheral lymph nodes. The strong amino acid sequence conservation of the cytoplasmic domain of L-selectin between humans and mice suggests an important role for this region. Deletion of the COOH-terminal 11 amino acids from the approximately 17 amino acid cytoplasmic domain of L-selectin eliminated binding of lymphocytes to HEV in the in vitro frozen section assay, and also abolished leukocyte rolling in vivo in exteriorized rat mesenteric venules, but did not alter the lectin activity of L-selectin. Pretreatment of cells with cytochalasin B, which disrupts actin microfilaments, also abolished adhesion without affecting carbohydrate recognition. Therefore, the cytoplasmic domain of L-selectin regulates leukocyte adhesion to endothelium independent of ligand recognition, by controlling cytoskeletal interactions and/or receptor avidity.

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