Characterization of a human homologue of the murine peripheral lymph node homing receptor.

Lymphocyte trafficking is a fundamental aspect of the immune system that allows B and T lymphocytes with diverse antigen recognition specificities to be exposed to various antigenic stimuli in spatially distinct regions of an organism. A lymphocyte adhesion molecule that is involved with this trafficking phenomenon has been termed the homing receptor. Previous work (Lasky, L., T. Yednock, M. Singer, D. Dowbenko, C. Fennie, H. Rodriguez, T. Nguyen, S. Stachel, and S. Rosen. 1989. Cell. 56:1045-1055) has characterized a cDNA clone encoding a murine homing receptor that is involved in trafficking of lymphocytes to peripheral lymph nodes. This molecule was found to contain a number of protein motifs, the most intriguing of which was a carbohydrate binding domain, or lectin, that is apparently involved in the adhesive interaction between murine lymphocytes and peripheral lymph node endothelium. In this study, we have used the murine cDNA clone to isolate a human homologue of this peripheral lymph node-specific adhesion molecule. The human receptor was found to be highly homologous to the murine receptor in overall sequence, but showed no sequence similarity to another surface protein that may be involved with human lymphocyte homing, the Hermes glycoprotein. The extracellular region of the human receptor contained an NH2 terminally located carbohydrate binding domain followed by an EGF-like domain and a domain containing two repeats of a complement binding motif. Transient cell transfection assays using the human receptor cDNA showed that it encoded a surface glycoprotein that cross reacted with a polyclonal antibody directed against the murine peripheral lymph node homing receptor. Interestingly, the human receptor showed a high degree of sequence homology to another human cell adhesion glycoprotein, the endothelial cell adhesion molecule ELAM.

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Characterization of the bovine peripheral lymph node homing receptor: a lectin cell adhesion molecule (LECAM)

European Journal of Immunology ◽

10.1002/eji.1830220227 ◽

1992 ◽

Vol 22 (2) ◽

pp. 469-476 ◽

Cited By ~ 18

Author(s):

Bruce Walcheck ◽

Michael White ◽

Sandy Kurk ◽

Takashi K. Kishimoto ◽

Mark A. Jutila

Keyword(s):

Cell Adhesion ◽

Lymph Node ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Peripheral Lymph Node ◽

Homing Receptor ◽

Lymph Node Homing ◽

Peripheral Lymph

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The Peripheral Lymph Node Homing Receptor: Tandem Structural and Functional Domains in a Novel Class of Adhesion Molecule

Cellular and Molecular Mechanisms of Inflammation ◽

10.1016/b978-0-12-150402-1.50007-x ◽

1991 ◽

pp. 61-89

Author(s):

Mark H. Siegelman ◽

Irving L. Weissman

Keyword(s):

Lymph Node ◽

Adhesion Molecule ◽

Functional Domains ◽

Peripheral Lymph Node ◽

Homing Receptor ◽

Lymph Node Homing ◽

Peripheral Lymph

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Identification of a human peripheral lymph node homing receptor: a rapidly down-regulated adhesion molecule.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.87.6.2244 ◽

1990 ◽

Vol 87 (6) ◽

pp. 2244-2248 ◽

Cited By ~ 251

Author(s):

T. K. Kishimoto ◽

M. A. Jutila ◽

E. C. Butcher

Keyword(s):

Lymph Node ◽

Adhesion Molecule ◽

Peripheral Lymph Node ◽

Homing Receptor ◽

Lymph Node Homing ◽

Peripheral Lymph

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

The Journal of Cell Biology ◽

10.1083/jcb.113.5.1213 ◽

1991 ◽

Vol 113 (5) ◽

pp. 1213-1221 ◽

Cited By ~ 183

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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Bovine γδ T cells express high levels of functional peripheral lymph node homing receptor (L-selectin)

International Immunology ◽

10.1093/intimm/6.1.81 ◽

1994 ◽

Vol 6 (1) ◽

pp. 81-91 ◽

Cited By ~ 24

Author(s):

Bruce Walcheck ◽

Mark A. Jutila

Keyword(s):

T Cells ◽

Lymph Node ◽

Γδ T Cells ◽

Peripheral Lymph Node ◽

Homing Receptor ◽

Lymph Node Homing ◽

Peripheral Lymph

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

The Journal of Cell Biology ◽

10.1083/jcb.114.2.343 ◽

1991 ◽

Vol 114 (2) ◽

pp. 343-349 ◽

Cited By ~ 208

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.

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The peripheral lymph node homing receptor, LECAM-1, is involved in CD18-independent adhesion of human neutrophils to endothelium

Biochemical and Biophysical Research Communications ◽

10.1016/0006-291x(91)90511-5 ◽

1991 ◽

Vol 174 (1) ◽

pp. 236-243 ◽

Cited By ~ 52

Author(s):

R. Hallmann ◽

M.A. Jutila ◽

C.W. Smith ◽

D.C. Anderson ◽

T.K. Kishimoto ◽

...

Keyword(s):

Lymph Node ◽

Human Neutrophils ◽

Peripheral Lymph Node ◽

Homing Receptor ◽

Lymph Node Homing ◽

Peripheral Lymph

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Regulation and lectin activity of the human neutrophil peripheral lymph node homing receptor

Blood ◽

10.1182/blood.v76.1.178.bloodjournal761178 ◽

1990 ◽

Vol 76 (1) ◽

pp. 178-183

Author(s):

MA Jutila ◽

TK Kishimoto ◽

EC Butcher

Keyword(s):

Lymph Node ◽

Cell Surface ◽

Human Neutrophil ◽

Human Lymphocytes ◽

Human Neutrophils ◽

Peripheral Lymph Node ◽

Homing Receptor ◽

Lymph Node Homing ◽

Peripheral Lymph ◽

Mannose 6 Phosphate

We characterize the nature and regulation of a human neutrophil cell surface antigen recognized by monoclonal antibodies (the DREG series) against a human lymphocyte peripheral lymph node homing receptor. Human neutrophils express high levels of the DREG antigen, whose expression is downregulated after treatment with phorbol myristate acetate, or the chemotactic factors C5a and FMLP. Interestingly, C5a treatment also downregulated the monocyte DREG antigen, but had no effect on expression of the lymphocyte molecule. Within 3 minutes after treatment with C5a, greater than 80% of neutrophil DREG antigen expression is lost, and essentially the molecule is completely removed from the cell surface by 5 minutes. The human neutrophil DREG antigen is 10 Kd larger than the lymphocyte molecule. These features are similar to those of the mouse neutrophil MEL-14 antigen (murine peripheral lymph node homing receptor). The mannose-6-phosphate rich phosphomannan (PPME) binds human lymphocytes via the DREG antigen. PPME also binds neutrophils, but little difference in binding is seen between unactivated and activated cells. We show that PPME binding to unactivated neutrophils is mediated primarily by a cation- and DREG antigen-dependent mechanism, whereas activated neutrophil-PPME binding is DREG antigen- and cation-independent, and may be due to the translocation of lysosomal mannose-6-phosphate receptors to the cell surface. The DREG antibodies offer powerful tools for analyzing the role of homing receptors in human neutrophil-endothelial cell interactions, and also may prove valuable in the clinical assessment of neutrophil activation.

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Regulation and lectin activity of the human neutrophil peripheral lymph node homing receptor

Blood ◽

10.1182/blood.v76.1.178.178 ◽

1990 ◽

Vol 76 (1) ◽

pp. 178-183 ◽

Cited By ~ 42

Author(s):

MA Jutila ◽

TK Kishimoto ◽

EC Butcher

Keyword(s):

Lymph Node ◽

Cell Surface ◽

Human Neutrophil ◽

Human Lymphocytes ◽

Human Neutrophils ◽

Peripheral Lymph Node ◽

Homing Receptor ◽

Lymph Node Homing ◽

Peripheral Lymph ◽

Mannose 6 Phosphate

Abstract We characterize the nature and regulation of a human neutrophil cell surface antigen recognized by monoclonal antibodies (the DREG series) against a human lymphocyte peripheral lymph node homing receptor. Human neutrophils express high levels of the DREG antigen, whose expression is downregulated after treatment with phorbol myristate acetate, or the chemotactic factors C5a and FMLP. Interestingly, C5a treatment also downregulated the monocyte DREG antigen, but had no effect on expression of the lymphocyte molecule. Within 3 minutes after treatment with C5a, greater than 80% of neutrophil DREG antigen expression is lost, and essentially the molecule is completely removed from the cell surface by 5 minutes. The human neutrophil DREG antigen is 10 Kd larger than the lymphocyte molecule. These features are similar to those of the mouse neutrophil MEL-14 antigen (murine peripheral lymph node homing receptor). The mannose-6-phosphate rich phosphomannan (PPME) binds human lymphocytes via the DREG antigen. PPME also binds neutrophils, but little difference in binding is seen between unactivated and activated cells. We show that PPME binding to unactivated neutrophils is mediated primarily by a cation- and DREG antigen-dependent mechanism, whereas activated neutrophil-PPME binding is DREG antigen- and cation-independent, and may be due to the translocation of lysosomal mannose-6-phosphate receptors to the cell surface. The DREG antibodies offer powerful tools for analyzing the role of homing receptors in human neutrophil-endothelial cell interactions, and also may prove valuable in the clinical assessment of neutrophil activation.

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