Kupffer cell-mediated recruitment of rat dendritic cells to the liver: Roles of N-acetylgalactosamine-specific sugar receptors

Background & Aims: Tissue recruitment of dendritic cells (DCs) is essential for antigen presentation. This study aimed to examine cellular and molecul ar mechanisms for DC recruitment to the liver. Methods: Purified rat DCs we re injected into circulation and their traffics were analyzed in normal and Kupffer cell-depleted rats by intravital confocal microscopy and immunohis tology. Affinities of DCs to sinusoidal cells were examined by a cell-bindi ng assay. DC precursor recruitment was induced by particulate injection. Re sults: Both DC precursors and DCs at the antigen-transporting stage could b e recruited to the liver, and their majority initially showed a selective b inding to Kupffer cells. In the Kupffer cell-depleted rats, DCs could neith er be recruited to the liver nor adhere to sinusoidal walls. Pretreatment w ith varied monosaccharides showed that sugar residues consisting of N-acety lgalactosamine were necessary for this binding. The binding was calcium-dep endent, implying the C-type lectin involvement. Furthermore, DCs could endo cytose N-acetylgalactosamine polymers in a receptor-specific manner. Conclu sions: The DC-Kupffer cell binding through N-acetylgalactosamine-specific C -type lectin-like receptors is crucial for DC recruitment to the liver. Rat DCs at least partly possess receptors for endocytosis of galactosylated an tigens. These DC receptors as well as Kupffer cell lectins are presumably r esponsible for this binding.