Preferential Induction of Peripheral Lymph Node Addressin on High Endothelial Venule-Like Vessels in the Active Phase of Ulcerative Colitis

Lichen planus (LP) is a chronic inflammatory mucocutaneous disease involving the oral mucosa and skin. Both oral LP (OLP) and cutaneous LP (CLP) are histopathologically characterized by dense subepithelial lymphocyte infiltrates; however, the mechanisms underlying lymphocyte recruitment to sites of LP lesions are not fully understood. Here, we assessed the induction of peripheral lymph node addressin (PNAd)-expressing high endothelial venule (HEV)-like vessels in 19 OLP and 17 CLP cases. To do so, we performed immunohistochemical staining for PNAd and CD34, followed by quantitative analysis. We also conducted triple immunohistochemistry for PNAd and either CD3 and CD20 or CD4 and CD8 to identify the lymphocyte subset preferentially recruited via HEV-like vessels. PNAd-expressing HEV-like vessels were induced in and around lymphocyte aggregates in all cases of OLP and in 10 of 17 CLP cases, and these vessels were more frequently observed in OLP relative to CLP. Although the number of T-cells attached per HEV-like vessel exceeded the number of B-cells in both OLP and CLP, the number of CD4+ T-cells attached was greater than the number of CD8+ T-cells only in OLP. These findings combined suggest that PNAd-expressing HEV-like vessels play a more important role in the pathogenesis of OLP compared with CLP.

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

The Journal of Cell Biology ◽

10.1083/jcb.109.1.421 ◽

1989 ◽

Vol 109 (1) ◽

pp. 421-427 ◽

Cited By ~ 60

Author(s):

B R Bowen ◽

T Nguyen ◽

L A Lasky

Keyword(s):

Cell Adhesion ◽

Lymph Node ◽

Adhesion Molecule ◽

Carbohydrate Binding ◽

Human Homologue ◽

Peripheral Lymph Node ◽

Homing Receptor ◽

Lymph Node Homing ◽

Peripheral Lymph ◽

Human 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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Cover Picture: Distinct molecular composition of blood and lymphatic vascular endothelial cell junctions establishes specific functional barriers within the peripheral lymph node - Eur. J. Immunol. 8/2008

European Journal of Immunology ◽

10.1002/eji.200890034 ◽

2008 ◽

Vol 38 (8) ◽

pp. NA-NA

Author(s):

Friederike Pfeiffer ◽

Varsha Kumar ◽

Stefan Butz ◽

Dietmar Vestweber ◽

Beat A. Imhof ◽

...

Keyword(s):

Lymph Node ◽

Endothelial Cell ◽

Vascular Endothelial Cell ◽

Molecular Composition ◽

Cell Junctions ◽

Vascular Endothelial ◽

Peripheral Lymph Node ◽

Peripheral Lymph

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Epidemiology of Peripheral Lymph Node Tuberculosis and Genotyping of M. tuberculosis Strains: A Case-Control Study

PLoS ONE ◽

10.1371/journal.pone.0132400 ◽

2015 ◽

Vol 10 (7) ◽

pp. e0132400 ◽

Cited By ~ 4

Author(s):

Chinmay Khandkar ◽

Zinta Harrington ◽

Peter J. Jelfs ◽

Vitali Sintchenko ◽

Claudia C. Dobler

Keyword(s):

Lymph Node ◽

Case Control Study ◽

Case Control ◽

Peripheral Lymph Node ◽

Peripheral Lymph ◽

Lymph Node Tuberculosis ◽

Control Study

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Demonstration that a lectin-like receptor (gp90MEL) directly mediates adhesion of lymphocytes to high endothelial venules of lymph nodes.

The Journal of Cell Biology ◽

10.1083/jcb.109.5.2463 ◽

1989 ◽

Vol 109 (5) ◽

pp. 2463-2469 ◽

Cited By ~ 48

Author(s):

J S Geoffroy ◽

S D Rosen

Keyword(s):

Lymph Node ◽

Lymphoid Organ ◽

Lymphoid Organs ◽

Surface Glycoprotein ◽

Lymphocyte Migration ◽

Peripheral Lymph Node ◽

Adhesive Interaction ◽

High Endothelial Venules ◽

Cell Surface Glycoprotein ◽

Peripheral Lymph

Lymphocyte migration from the blood into most secondary lymphoid organs is initiated by a highly selective adhesive interaction with the endothelium of specialized blood vessels known as high endothelial venules (HEV). The propensity of lymphocytes to migrate to particular lymphoid organs is known as lymphocyte homing, and the receptors on lymphocytes that dictate interactions with HEV at particular anatomical sites are designated "homing receptors". Based upon antibody blockade experiments and cell-type distribution studies, a prominent candidate for the peripheral lymph node homing receptor in mouse is the approximately 90-kD cell surface glycoprotein (gp90MEL) recognized by the monoclonal antibody MEL-14. Previous work, including sequencing of a cDNA encoding for this molecule, supports the possibility that gp90MEL is a calcium-dependent lectin-like receptor. Here, we show that immunoaffinity-purified gp90MEL interacts in a sugar-inhibitable manner with sites on peripheral lymph node HEV and prevents attachment of lymphocytes. Lymphocyte attachment to HEV in Peyer's patches, a gut-associated lymphoid organ, is not affected by gp90MEL. The results demonstrate that gp90MEL, as a lectin-like receptor, directly bridges lymphocytes to the endothelium.

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