title: CD44 binds to macrophage mannose receptor on lymphatic endothelium and supports lymphocyte migration via afferent lymphatics.
abstract: BACKGROUND
  Macrophage mannose receptor (MRC) is one of the few molecules known to be involved in lymphocyte trafficking via the lymphatic vessels. In endothelial cells of efferent lymphatics, it binds L-selectin on lymphocytes. In afferent lymphatics, MRC mediates trafficking of both normal and malignant L-selectin-negative cells to the draining lymph nodes.
  
  
  OBJECTIVE
  This work was designed to search for additional lymphocyte ligands of MRC to elucidate how lymphocytes migrate into the draining lymph nodes.
  
  
  RESULTS
  Using immunoprecipitation and binding studies with natural and recombinant proteins, we show that MRC and CD44 can interact with each other. Fine mapping revealed that the cysteine-rich domain of MRC binds to the chondroitin sulfate side chains of CD44. In vivo homing experiments with MRC- and CD44-deficient mice verified that MRC and CD44 function as a receptor-ligand pair in supporting lymphocyte migration via the afferent lymphatics into the draining lymph nodes.
  
  
  CONCLUSIONS
  These data identify a new counter-receptor for MRC and reveal CD44 as a new molecule involved in the poorly understood process of lymphocyte transit via the lymphatic vasculature.
authors.affiliation: MediCity Research Laboratory, University of Turku, FIN-20520 Turku, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Salmi
authors.forename: Marika
authors.initials: M
authors.lastname: Karikoski
authors.forename: Kati
authors.initials: K
authors.lastname: Elima
authors.forename: Pia
authors.initials: P
authors.lastname: Rantakari
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte; D002809:Chondroitin Sulfates / Q000378:metabolism; D004729:Endothelium, Lymphatic / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C497483:CD44 protein, human; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D008024:Ligands; C573543:MRC1 protein, human; C581013:MRC1 protein, mouse; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D002809:Chondroitin Sulfates
keywords: endothelium; leukocyte; lymphatics; lymphocytes; migration; traffic