Selective expression of sialyl-Lewis x and Lewis a epitopes, putative ligands for L-selectin, on peripheral lymph-node high endothelial venules.
Timo Paavonen, Risto Renkonen
Abstract
Timo Paavonen, Risto Renkonen
Abstract
High endothelial venules (HEV) lined by the high endothelium are the sites where leukocytes enter into the lymph nodes from the blood. Lymphocyte homing into lymph nodes is organ-selective, i.e., different molecules are involved in the lymphocyte homing to peripheral nodes compared with mucosa associated lymphoid tissue. The traffic into peripheral nodes is regulated by the expression of L-selectin on leukocytes and its ligand on HEVs. The ligand for L-selectin is suggested to be a 50, 90, or 105 kd glycoprotein, which is sulfated, fucosylated, and sialylated. The two other members of the selectin family (E- and P-selectin) recognize sialyl-Lewis x and -Lewis a (sLex and sLea, respectively) carbohydrate motifs, and there is preliminary data suggesting that this would also be the case for L-selectin. We have initiated a study to identify the expression of these sialylated structures on endothelial surfaces. We present data that show that HEVs in peripheral nodes, but not in the mucosa-associated lymphoid tissue, express large quantities of sLex and sLea identified by MAbs in immunohistology. Endothelium in capillaries or larger vessels in non-lymphoid tissues do not react with anti-sLex or -Lea mAbs. Only 1-2% of the lymphocytes in the peripheral blood express sLex and so far only the skin-homing lymphocytes are known to be sLex positive in larger quantities. We show that in many occasions the B cells in the peripheral lymph-node germinal centers are also sLex-, but not sLea-positive, and provide evidence of the restricted pattern of sLex and sLea expression on peripheral lymph-node HEVs. We propose that they are at least parts of the ligand for L-selectin.
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High endothelial venules (HEV) lined by the high endothelium are the sites where leukocytes enter into the lymph nodes from the blood. Lymphocyte homing into lymph nodes is organ-selective, i.e., different molecules are involved in the lymphocyte homing to peripheral nodes compared with mucosa associated lymphoid tissue. The traffic into peripheral nodes is regulated by the expression of L-selectin on leukocytes and its ligand on HEVs. The ligand for L-selectin is suggested to be a 50, 90, or 105 kd glycoprotein, which is sulfated, fucosylated, and sialylated. The two other members of the selectin family (E- and P-selectin) recognize sialyl-Lewis x and -Lewis a (sLex and sLea, respectively) carbohydrate motifs, and there is preliminary data suggesting that this would also be the case for L-selectin. We have initiated a study to identify the expression of these sialylated structures on endothelial surfaces. We present data that show that HEVs in peripheral nodes, but not in the mucosa-associated lymphoid tissue, express large quantities of sLex and sLea identified by MAbs in immunohistology. Endothelium in capillaries or larger vessels in non-lymphoid tissues do not react with anti-sLex or -Lea mAbs. Only 1-2% of the lymphocytes in the peripheral blood express sLex and so far only the skin-homing lymphocytes are known to be sLex positive in larger quantities. We show that in many occasions the B cells in the peripheral lymph-node germinal centers are also sLex-, but not sLea-positive, and provide evidence of the restricted pattern of sLex and sLea expression on peripheral lymph-node HEVs. We propose that they are at least parts of the ligand for L-selectin.
Key concepts: Lymphocyte homing receptor, High endothelial venules, Homing (biology), Sialyl-Lewis X, Lymph, Pathology, Addressin, Lymphatic system