Purification of L-selectin ligands synthesised by rat peripheral lymph nodes and cultured high endothelial cells

The tissue localization or "homing" of circulating lymphocytes is directed in part by specialized vessels that define sites of lymphocyte exit from the blood. In peripheral lymph nodes, mucosal lymphoid tissues (Peyer's patches and appendix), and sites of chronic inflammation, for example, lymphocytes leave the blood by adhering to and migrating between those endothelial cells lining postcapillary high endothelial venules (HEV). Functional analyses of lymphocyte interactions with HEV have shown the lymphocytes can discriminate between HEV in different tissues, indicating that HEV express tissue-specific determinants or address signals for lymphocyte recognition. We recently described such a tissue-specific "vascular addressin" that is selectively expressed by endothelial cells supporting lymphocyte extravasation into mucosal tissues and that appears to be required for mucosa-specific lymphocyte homing (Streeter, P. R., E. L. Berg, B. N. Rouse, R. F. Bargatze, and E. C. Butcher. 1988. Nature (Lond.). 331:41-46). Here we document the existence and tissue-specific distribution of a distinct HEV differentiation antigen. Defined by monoclonal antibody MECA-79, this antigen is expressed at high levels on the lumenal surface and in the cytoplasm of HEV in peripheral lymph nodes. By contrast, although MECA-79 stains many HEV in the mucosal Peyer's patches, expression in most cases is restricted to the perivascular or ablumenal aspect of these venules. In the small intestine lamina propria, a mucosa-associated site that supports the extravasation of lymphocytes, venules do not stain with MECA-79. Finally, we demonstrate that MECA-79 blocks binding of both normal lymphocytes and a peripheral lymph node-specific lymphoma to peripheral lymph node HEV in vitro and that it also inhibits normal lymphocyte homing to peripheral lymph nodes in vivo without significantly influencing lymphocyte interactions with Peyer's patch HEV in vitro or in vivo. Thus, MECA-79 defines a novel vascular addressin involved in directing lymphocyte homing to peripheral lymph nodes.

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STUDIES OF THE LYMPHATIC TISSUE

Journal of Experimental Medicine ◽

10.1084/jem.49.3.361 ◽

1929 ◽

Vol 49 (3) ◽

pp. 361-386 ◽

Cited By ~ 13

Author(s):

Wilhelm Ehrich

Keyword(s):

Endothelial Cells ◽

Lymph Nodes ◽

Plasma Cells ◽

Giant Cells ◽

Interstitial Tissue ◽

Lymphatic Tissue ◽

Cervical Lymph Nodes ◽

Peripheral Lymph ◽

Small Doses ◽

Primary Reactions

In 87 rabbits, some of which received intravenously at various intervals small, and some large, doses of killed staphylococci, the following findings were obtained. 1. There occurred a hyperplasia of lymph nodes, spleen and thymus, that is to say, a status thymicolymphaticus. This phenomenon is explained as due to immediate local irritation caused by bacteria and their products and by certain "toxins" partly of exogenous, partly of endogenous, origin. 2. The lymphocytosis which appeared was parallel in time and degree with the hyperplasia of the peripheral lymph nodes (axillary, popliteal and cervical lymph nodes) and probably originated in the pseudo-secondary nodules of these nodes. 3. There occurred intense mesenchymal reaction in the vascular connective tissue of the lungs, liver and spleen and after large doses slighter ones in adrenals, kidneys and heart. These reactions correspond with Oeller's adventitial reactions and Siegmund's intima proliferations. In the interstitial tissue of these organs as well as in the walls of the minor vessels proliferations of cells, partly of the type of lymphocytes and plasma cells, partly of that of histiocytes and reticulo-endothelial cells, appeared, which, after large doses, were mixed with many giant cells of Langerhans' type. After small doses lymphocytes and plasma cells predominated, after large doses histiocytes and reticulo-endothelial cells. Because these reactions occurred immediately after the first injection, they can be regarded as primary reactions of the organism to bacteria and their products.

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Sulphated endothelial ligands for L-selectin in lymphocyte homing and inflammation

Biochemical Society Transactions ◽

10.1042/bst0310313 ◽

2003 ◽

Vol 31 (2) ◽

pp. 313-317 ◽

Cited By ~ 30

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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