Human dendritic cells shed a functional, soluble form of the mannose receptor

Human monocyte-derived dendritic cells (DC) use mannose receptor (MR)-media ted endocytosis for efficient antigen capture and targeting to the endosoma l/lysosomal compartment Active biosynthesis of the MR takes place in such c ells. We now report that a substantial percentage (up to 20%) of these newl y 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. Th e addition of the inflammatory mediator lipopolysaccharide (LPS) to DC, kno wn to induce maturation, strongly reduced MR synthesis, expression and shed ding of the MR. The sMR is similar to 10 kDa smaller than the membrane-boun d form, but contains an intact N-terminus, indicating the lack of the cytop lasmic 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 inf lammation to other parts of the body. Whether that contributes to the gener ation of immune responses remains to be determined.