The Journal of Experimental Medicine
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Published 8 October 2001. doi:10.1084/jem.194.8.1033
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© The Rockefeller University Press, 0022-1007/2001/10/1033/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 8, October 15, 2001 1033-1042

Original Article

Mannose Receptor Is a Novel Ligand for L-Selectin and Mediates Lymphocyte Binding to Lymphatic Endothelium

Heikki Irjalaa, Eva-Liz Johanssona, Reidar Grenmanb, Kalle Alanenc, Marko Salmia, and Sirpa Jalkanena
a MediCity Research Laboratory, Department of Medical Microbiology, and National Public Health Institute, Department in Turku, and the Departments of
b Otorhinolaryngology–Head and Neck Surgery, University of Turku, FIN-20520 Turku, Finland
c Pathology, University of Turku, FIN-20520 Turku, Finland

Correspondence to: Sirpa Jalkanen, MediCity Research Laboratory, University of Turku, Tykistokatu 6, FIN-20520 Turku, Finland. Tel:358-2-333-7007 Fax:358-2-333-7000 E-mail:sirpa.jalkanen{at}utu.fi.

Continuous lymphocyte recirculation between blood and lymphoid tissues forms a basis for the function of the immune system. Lymphocyte entrance from the blood into the tissues has been thoroughly characterized, but mechanisms controlling lymphocyte exit from the lymphoid tissues via efferent lymphatics have remained virtually unknown. In this work we have identified mannose receptor (MR) on human lymphatic endothelium and demonstrate its involvement 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 pair. On the other hand, L-selectin binds to peripheral lymph node addressins (PNAds) on high endothelial venules (HEVs) that are sites where lymphocytes enter the lymphatic organs. Interestingly, MR is absent from HEVs and PNAds from lymphatic endothelium. Thus, lymphocyte L-selectin uses distinct ligand 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.

Key Words: lymphatics, lymphocyte recirculation, cancer metastasis, endothelium, lymph node


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