The macrophage C-type lectin specific for galactose/N-acetylgalactosamine is an endocytic receptor expressed on monocyte-derived immature dendritic cells.
Lectins on antigen presenting cells are potentially involved in the antigen uptake and the cellular recognition and trafficking. Serial analysis of gene expression in monocyte-derived dendritic cells (DCs), monocytes, and macrophages revealed that 7 of the 19 C-type lectin mRNA were present in immature DCs. Two of these, the macrophage mannose receptor and the macrophage lectin specific for galactose/N-acetylgalactosamine (MGL), were found only in immature DCs, as confirmed by reverse transcriptase-PCR and flow cytometric analysis. By subcloning and sequencing the amplified mRNA, we obtained nucleotide sequences encoding seven different human MGL (hMGL) subtypes, which were apparently derived from alternatively spliced mRNA. In addition, the hMGL gene locus on human chromosome 17p13 contains one gene. A single nucleotide polymorphism was identified at a position in exon 3 that corresponds to the cytoplasmic region proximal to the transmembrane domain. Of all the splicing variants, the hMGL variant 6C was expressed at the highest levels on immature DCs from all donors tested. Immature DCs could incorporate alpha-GalNAc-modified soluble acrylamide polymers, and this was significantly inhibited by pretreatment of the cells with an anti-hMGL monoclonal antibody that blocks the lectin-carbohydrate interaction. We propose that hMGL is a marker of imDCs and that it functions as an endocytic receptor for glycosylated antigens.
Higashi
Nobuaki
N
Graduate School of Pharmaceutical Sciences and the Department of Molecular Preventive Medicine, School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Fujioka
Kouki
K
Denda-Nagai
Kaori
K
Hashimoto
Shin-Ichi
S
Nagai
Shigenori
S
Sato
Taku
T
Fujita
Yuko
Y
Morikawa
Akiko
A
Tsuiji
Makoto
M
Miyata-Takeuchi
Megumi
M
Sano
Yoshihiko
Y
Suzuki
Noriko
N
Yamamoto
Kazuo
K
Matsushima
Kouji
K
Irimura
Tatsuro
T
D000116:Acetylgalactosamine / Q000378:metabolism*; D017398:Alternative Splicing; D001483:Base Sequence; D004247:DNA; D003713:Dendritic Cells / Q000378:metabolism*; D004705:Endocytosis; D005091:Exons; D005690:Galactose / Q000378:metabolism*; D006801:Humans; D007438:Introns; D037102:Lectins / Q000378:metabolism*; D037181:Lectins, C-Type; D008264:Macrophages / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009000:Monocytes / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D037102:Lectins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D004247:DNA; D000116:Acetylgalactosamine; D005690:Galactose