Human dendritic cells shed a functional, soluble form of the mannose receptor.
Human monocyte-derived dendritic cells (DC) use mannose receptor (MR)-mediated endocytosis for efficient antigen capture and targeting to the endosomal/lysosomal compartment. Active biosynthesis of the MR takes place in such cells. We now report that a substantial percentage (up to 20%) of these newly synthesized MR are secreted into the culture medium. The secretion of the soluble MR (sMR) was found to be proportional to the rate of synthesis. The addition of the inflammatory mediator lipopolysaccharide (LPS) to DC, known to induce maturation, strongly reduced MR synthesis, expression and shedding of the MR. The sMR is approximately 10 kDa smaller than the membrane-bound form, but contains an intact N-terminus, indicating the lack of the cytoplasmic and transmembrane region. The sMR appeared to be directly generated from the cell-bound form, indicative of proteolytic cleavage. Importantly, the sMR has maintained its mannose-binding properties since it was capable of binding a mannosylated ligand. The high amount of sMR released by DC and its ability to bind mannosylated ligand might indicate that this molecule plays a role in the transport of mannosylated proteins from the site of inflammation to other parts of the body. Whether that contributes to the generation of immune responses remains to be determined.
Jordens
R
R
Department of Immunohaematology and Blood Bank, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, 2300 RC Leiden, The Netherlands.
Thompson
A
A
Amons
R
R
Koning
F
F
D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D037181:Lectins, C-Type; D008070:Lipopolysaccharides / Q000494:pharmacology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011233:Precipitin Tests; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D012995:Solubility
D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface