Mannose receptor is a novel ligand for L-selectin and mediates lymphocyte binding to lymphatic endothelium

Continuous lymphocyte recirculation between blood and lymphoid tissues form s a basis for the function of the immune system. Lymphocyte entrance from t he blood into the tissues has been thoroughly characterized, but mechanisms controlling lymphocyte exit from the lymphoid tissues via efferent lymphat ics have remained virtually unknown. In this work we have identified mannos e receptor (MR) on human lymphatic endothelium. and demonstrate its involve ment in binding of lymphocytes to lymphatic vessels. We also show that the binding requires L-selectin, and L-selectin and MR form a receptor-ligand p air. On the other hand, L-selectin binds to peripheral lymph node addressin s (PNAds) on high endothelial venules (HEVS) that are sites where lymphocyt es enter the lymphatic organs. Interestingly, MR is absent from HEVs and PN Ads from lymphatic endothelium. Thus, lymphocyte L-selectin uses distinct l igand molecules to mediate binding at sites of lymphocyte entrance and exit within lymph nodes. Taken together, interaction between L-selectin and MR is the first molecularly defined mechanism mediating lymphocyte binding to lymphatic endothelium.