scholarly journals 6-C-kine (SLC), a Lymphocyte Adhesion-triggering Chemokine Expressed by High Endothelium, Is an Agonist for the MIP-3β Receptor CCR7

1998 ◽  
Vol 141 (4) ◽  
pp. 1053-1059 ◽  
Author(s):  
James J. Campbell ◽  
Edward P. Bowman ◽  
Kristine Murphy ◽  
Kenneth R. Youngman ◽  
Michael A. Siani ◽  
...  
Keyword(s):  
Lymphoid Tissue ◽  
Memory T Cells ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Lymphocyte Adhesion ◽  
Common Receptor ◽  
Circulating Lymphocytes ◽  
Stromal Cell Derived Factor ◽  
Mouse Lymphocytes

The β chemokine known as 6-C-kine, secondary lymphoid-tissue chemokine (SLC), TCA4, or Exodus-2 (herein referred to as 6CK/SLC) can trigger rapid integrin-dependent arrest of lymphocytes rolling under physiological shear and is highly expressed by high endothelial venules, specialized vessels involved in lymphocyte homing from the blood into lymph nodes and Peyer's patches. We show that 6CK/SLC is an agonist for the lymphocyte chemoattractant receptor, CCR7 (EBI-1, BLR-2), previously described as a receptor for the related β chemokine MIP-3β (ELC or Exodus-3). Moreover, 6CK/SLC and MIP-3β attract the same major populations of circulating lymphocytes, including naive and memory T cells > B cells (but not natural killer cells); desensitization to MIP-3β inhibits lymphocyte chemotaxis to 6CK/SLC but not to the α chemokine SDF-1 (stromal cell–derived factor); and 6CK/SLC competes for MIP-3β binding to resting mouse lymphocytes. The findings suggest that the majority of circulating lymphocytes respond to 6CK/SLC and MIP-3β in large part through their common receptor CCR7 and that these molecules may be important mediators of physiological lymphocyte recirculation in vivo.

scholarly journals Comprehensive analysis of lymph node stroma-expressed Ig superfamily members reveals redundant and nonredundant roles for ICAM-1, ICAM-2, and VCAM-1 in lymphocyte homing

Blood ◽  
2010 ◽  
Vol 116 (6) ◽  
pp. 915-925 ◽  
Author(s):  
Rémy T. Boscacci ◽  
Friederike Pfeiffer ◽  
Kathrin Gollmer ◽  
Ana Isabel Checa Sevilla ◽  
Ana Maria Martin ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Lymphocyte Adhesion ◽  
Peripheral Lymph ◽  
The Individual ◽  
Cell Adhesion Molecule 1

Abstract Although it is well established that stromal intercellular adhesion molecule-1 (ICAM-1), ICAM-2, and vascular cell adhesion molecule-1 (VCAM-1) mediate lymphocyte recruitment into peripheral lymph nodes (PLNs), their precise contributions to the individual steps of the lymphocyte homing cascade are not known. Here, we provide in vivo evidence for a selective function for ICAM-1 > ICAM-2 > VCAM-1 in lymphocyte arrest within noninflamed PLN microvessels. Blocking all 3 CAMs completely inhibited lymphocyte adhesion within PLN high endothelial venules (HEVs). Postarrest extravasation of T cells was a 3-step process, with optional ICAM-1–dependent intraluminal crawling followed by rapid ICAM-1– or ICAM-2–independent diapedesis and perivascular trapping. Parenchymal motility of lymphocytes was modestly reduced in the absence of ICAM-1, while ICAM-2 and α4-integrin ligands were not required for B-cell motility within follicles. Our findings highlight nonredundant functions for stromal Ig family CAMs in shear-resistant lymphocyte adhesion in steady-state HEVs, a unique role for ICAM-1 in intraluminal lymphocyte crawling but redundant roles for ICAM-1 and ICAM-2 in lymphocyte diapedesis and interstitial motility.

scholarly journals High endothelial venule binding as a predictor of the dissemination of passaged murine lymphomas.

1987 ◽  
Vol 166 (4) ◽  
pp. 1125-1131 ◽  
Author(s):  
R F Bargatze ◽  
N W Wu ◽  
I L Weissman ◽  
E C Butcher
Keyword(s):  
Lymph Nodes ◽  
Growth Patterns ◽  
Normal Lymphocyte ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Vitro Assay ◽  
Surface Receptors ◽  
Circulating Lymphocytes

It has long been postulated that normal lymphocyte homing mechanisms help determine the metastatic spread of lymphoid neoplasms. The traffic of normal lymphocytes is controlled in part by the regulated expression of surface receptors for high endothelial venules (HEV), specialized venules that mediate the extravasation of circulating lymphocytes from the blood into lymphoid organs and sites of chronic inflammation. Here we have compared the in vivo growth patterns of HEV-binding vs. nonbinding murine lymphomas passaged intramuscularly into syngeneic recipients. We report that lymphomas that bind well to HEV (as assessed in a quantitative in vitro assay) disseminate widely via the blood, involving all lymph node groups symmetrically. Although both HEV-binding and nonbinding lymphomas gain access to the blood, gross involvement of lymph nodes by nonbinding lymphomas is limited to nodes draining local tumor at the site of injection, a prominent feature of these lymphomas; distant lymph nodes are not enlarged. The results suggest that the expression of functional receptors for HEV either controls the hematogenous dissemination of malignant lymphocyte populations to HEV-bearing organs, or is coregulated with factors determining this metastatic behavior. The findings support the concept that normal lymphocyte homing mechanisms are important to the spread of leukemias and lymphomas.

scholarly journals Lymphocyte homing into lymph nodes: in vitro demonstration of the selective affinity of recirculating lymphocytes for high-endothelial venules.

1976 ◽  
Vol 144 (3) ◽  
pp. 828-833 ◽  
Author(s):  
H B Stamper ◽  
J J Woodruff
Keyword(s):  
Lymph Nodes ◽  
In Vitro Model ◽  
Lymphocyte Homing ◽  
High Endothelial Venules ◽  
Vascular Endothelia ◽  
Vitro Model ◽  
Mouse Lymphocytes

An in vitro model is described for studying the interaction between lymphocytes and high-endothelial venules (HEV) of lymph nodes. Rat or mouse lymphocytes which were layered over fixed sections of syngeneic lymph nodes adhered selectively to the endothelium of HEV but did not bind to other vascular endothelia. Evidence is presented that adherence to HEV in vitro is a property of recirculating lymphocytes and not a characteristic of cells which are unable to home into lymph nodes in vivo.

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.

scholarly journals The Role of Chemokines in the Microenvironmental Control of T versus B Cell Arrest in Peyer's Patch High Endothelial Venules

2000 ◽  
Vol 191 (1) ◽  
pp. 77-88 ◽  
Author(s):  
R.A. Warnock ◽  
J.J. Campbell ◽  
M.E. Dorf ◽  
A. Matsuzawa ◽  
L.M. McEvoy ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Peyer’S Patch ◽  
Peyer's Patch ◽  
Target Domain ◽  
High Endothelial Venules ◽  
Circulating Lymphocytes ◽  
Cell Arrest

Chemokines have been hypothesized to contribute to the selectivity of lymphocyte trafficking not only as chemoattractants, but also by triggering integrin-dependent sticking (arrest) of circulating lymphocytes at venular sites of extravasation. We show that T cells roll on most Peyer's patch high endothelial venules (PP-HEVs), but preferentially arrest in segments displaying high levels of luminal secondary lymphoid tissue chemokine (SLC) (6Ckine, Exodus-2, thymus-derived chemotactic agent 4 [TCA-4]). This arrest is selectively inhibited by functional deletion (desensitization) of CC chemokine receptor 7 (CCR7), the receptor for SLC and for macrophage inflammatory protein (MIP)-3β (EBV-induced molecule 1 ligand chemokine [ELC]), and does not occur in mutant DDD/1 mice that are deficient in these CCR7 ligands. In contrast, pertussis toxin–sensitive B cell sticking does not require SLC or MIP-3β signaling, and occurs efficiently in SLClow/− HEV segments in wild-type mice, and in the SLC-negative HEVs of DDD/1 mice. Remarkably, sites of T and B cell firm adhesion are segregated in PPs, with HEVs supporting B cell accumulation concentrated in or near follicles, the target domain of most B cells entering PPs, whereas T cells preferentially accumulate in interfollicular HEVs. Our findings reveal a fundamental difference in signaling requirements for PP-HEV recognition by T and B cells, and describe an unexpected level of specialization of HEVs that may allow differential, segmental control of lymphocyte subset recruitment into functionally distinct lymphoid microenvironments in vivo.

In vitro analysis of the homing properties of human lymphocytes: developmental regulation of functional receptors for high endothelial venules

Blood ◽  
1985 ◽  
Vol 66 (3) ◽  
pp. 577-582
Author(s):  
ST Jalkanen ◽  
EC Butcher
Keyword(s):  
Human Lymphocyte ◽  
In Vitro Model ◽  
Human Lymphocytes ◽  
Surrounding Tissue ◽  
Lymphoid Tissues ◽  
High Endothelial Venules ◽  
Circulating Lymphocytes ◽  
Vitro Model

Circulating lymphocytes leave the blood by binding to specialized high endothelial cells lining postcapillary venules in lymphoid organs or sites of chronic inflammations, migrating through the vessel wall into the surrounding tissue. The capacity of lymphocytes to recognize and bind to high endothelial venules (HEVs) is thus central to the overall process of lymphocyte traffic and recirculation. We show that viable human lymphocytes bind selectively to HEVs in frozen sections of normal human lymph nodes, thus defining a simple in vitro model for the study of human lymphocyte homing properties. Optimal conditions for the quantitative analysis of lymphocyte-HEV interaction are described. Furthermore, by using this assay, we demonstrate that the ability of human lymphocyte populations to bind to HEVs parallels their presumed migratory status in vivo. Thus, thymocytes and bone marrow cells, which are sessile in vivo, bind poorly to HEVs in comparison with mature circulating lymphocytes in peripheral blood or in peripheral lymphoid tissues. These results indicate that HEV-binding ability is a regulated property of mature lymphocytes and, as demonstrated previously in animal models, probably plays a fundamental role in controlling lymphocyte traffic in humans. The in vitro model of lymphocyte-HEV interaction thus provides a unique means to assay the migratory properties of normal and neoplastic human lymphocyte subsets, to analyze the role of lymphocyte traffic mechanisms in normal and pathologic inflammatory reactions, and to define some of the molecular mechanisms responsible for the control of lymphocyte migration and positioning in humans.

Rap1 controls lymphocyte adhesion cascade and interstitial migration within lymph nodes in RAPL-dependent and -independent manners

Blood ◽  
2010 ◽  
Vol 115 (4) ◽  
pp. 804-814 ◽  
Author(s):  
Yukihiko Ebisuno ◽  
Koko Katagiri ◽  
Tomoya Katakai ◽  
Yoshihiro Ueda ◽  
Tomomi Nemoto ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Critical Role ◽  
Small Gtpase ◽  
High Endothelial Venules ◽  
Lymphocyte Adhesion ◽  
Peripheral Lymph ◽  
Directional Movement ◽  
Lymphocyte Motility

Abstract The small GTPase Rap1 and its effector RAPL regulate lymphocyte adhesion and motility. However, their precise regulatory roles in the adhesion cascade preceding entry into lymph nodes and during interstitial migration are unclear. Here, we show that Rap1 is indispensably required for the chemokine-triggered initial arrest step of rolling lymphocytes through LFA-1, whereas RAPL is not involved in rapid arrest. RAPL and talin play a critical role in stabilizing lymphocyte arrest to the endothelium of blood vessels under flow or to the high endothelial venules of peripheral lymph nodes in vivo. Further, mutagenesis and peptide studies suggest that release of a trans-acting restraint from the β2 cytoplasmic region of LFA-1 is critical for Rap1-dependent initial arrest. Rap1 or RAPL deficiency severely impaired lymphocyte motility over lymph node stromal cells in vitro, and RAPL deficiency impaired high-velocity directional movement within lymph nodes. These findings reveal the several critical steps of Rap1, which are RAPL-dependent and -independent, in lymphocyte trafficking.

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.

scholarly journals In vitro analysis of the homing properties of human lymphocytes: developmental regulation of functional receptors for high endothelial venules

Blood ◽  
1985 ◽  
Vol 66 (3) ◽  
pp. 577-582 ◽  
Author(s):  
ST Jalkanen ◽  
EC Butcher
Keyword(s):  
Human Lymphocyte ◽  
In Vitro Model ◽  
Human Lymphocytes ◽  
Surrounding Tissue ◽  
Lymphoid Tissues ◽  
High Endothelial Venules ◽  
Circulating Lymphocytes ◽  
Vitro Model

Abstract Circulating lymphocytes leave the blood by binding to specialized high endothelial cells lining postcapillary venules in lymphoid organs or sites of chronic inflammations, migrating through the vessel wall into the surrounding tissue. The capacity of lymphocytes to recognize and bind to high endothelial venules (HEVs) is thus central to the overall process of lymphocyte traffic and recirculation. We show that viable human lymphocytes bind selectively to HEVs in frozen sections of normal human lymph nodes, thus defining a simple in vitro model for the study of human lymphocyte homing properties. Optimal conditions for the quantitative analysis of lymphocyte-HEV interaction are described. Furthermore, by using this assay, we demonstrate that the ability of human lymphocyte populations to bind to HEVs parallels their presumed migratory status in vivo. Thus, thymocytes and bone marrow cells, which are sessile in vivo, bind poorly to HEVs in comparison with mature circulating lymphocytes in peripheral blood or in peripheral lymphoid tissues. These results indicate that HEV-binding ability is a regulated property of mature lymphocytes and, as demonstrated previously in animal models, probably plays a fundamental role in controlling lymphocyte traffic in humans. The in vitro model of lymphocyte-HEV interaction thus provides a unique means to assay the migratory properties of normal and neoplastic human lymphocyte subsets, to analyze the role of lymphocyte traffic mechanisms in normal and pathologic inflammatory reactions, and to define some of the molecular mechanisms responsible for the control of lymphocyte migration and positioning in humans.

scholarly journals Biology of chemokine and classical chemoattractant receptors: differential requirements for adhesion-triggering versus chemotactic responses in lymphoid cells.

1996 ◽  
Vol 134 (1) ◽  
pp. 255-266 ◽  
Author(s):  
J J Campbell ◽  
S Qin ◽  
K B Bacon ◽  
C R Mackay ◽  
E C Butcher
Keyword(s):  
T Cells ◽  
Chemokine Receptors ◽  
Lymphoid Cells ◽  
Receptor Expression ◽  
Lymphocyte Adhesion ◽  
Formyl Peptide ◽  
Circulating Lymphocytes ◽  
Strong Adhesion ◽  
Alpha4beta1 Integrin

Several chemoattractant receptors can support agonist-induced, integrin-dependent arrest of rolling neutrophils in inflamed venules in vivo, as well as subsequent crawling into tissues. It has been hypothesized that receptors of the Galpha(i)-linked chemoattractant subfamilies, especially receptors for chemokines, may mediate parallel activation-dependent arrest of homing lymphocyte subsets. However, although several chemokines can attract subsets of B or T cells, robust chemoattractant triggering of resting lymphocyte adhesion to vascular ligands has not been observed. To study the biology of individual leukocyte chemoattractant receptors in a defined lymphoid environment, mouse L1/2 pre-B cells and/or human Jurkat T cells were transfected with alpha (IL-8 receptor A) or beta (MIP-1alpha/CC-CKR-1) chemokine receptors, or with the classical chemoattractant C5a (C5aR) or formyl peptide receptors (fPR). All receptors supported robust agonist-dependent alpha4beta1 integrin-mediated adhesion of lymphocytes to VCAM-1. L1/2 cells cotransfected with fPR and beta7 integrin were also induced to bind MAdCAM-1, suggesting common mechanisms coupling chemoattractant receptors to activation of distinct integrins. Adhesion was rapid but transient, with spontaneous reversion to unstimulated levels within 5 min after peak binding. When observed under flow conditions, alpha4beta1-mediated arrest occurred within seconds after initiation of contact and rolling of IL-8RA transfectants on VCAM-1/IL-8 co-coated surface; and arrest reversed spontaneously after a mean of 5 min with a return to rolling behavior. Each of the receptors also conferred agonist-specific chemotaxis; however, whereas strong adhesion required simultaneous occupancy of many receptors with maximal responses above the Kd, chemotaxis in each case was suppressed at high agonist concentrations. The findings indicate that alpha and beta chemokine as well as classical chemoattractant receptors can trigger robust adhesion as well as directed migration of lymphoid cells, but that the requirements for and kinetics of adhesion triggering and chemotaxis are distinct, thus permitting their independent regulation. They suggest that the discordance between proadhesive and chemoattractant responses of circulating lymphocytes to many chemokines may reflect quantitative aspects of receptor expression and/or coupling rather than qualitative differences in receptor signaling.

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