title: Functional comparison of the mouse DC-SIGN, SIGNR1, SIGNR3 and Langerin, C-type lectins.
abstract: The mouse (m) DC-SIGN family consists of several homologous type II transmembrane proteins located in close proximity on chromosome 8 and having a single carboxyl terminal carbohydrate recognition domain. We first used transfected non-macrophage cell lines to compare the polysaccharide and microbial uptake capacities of three of these lectins--DC-SIGN, SIGNR1 and SIGNR3--to another homologue mLangerin. Each molecule shares a potential mannose-recognition EPN-motif in its carbohydrate recognition domain. Using an anti-Tag antibody to follow Tag-labeled transfectants, we found that each molecule could be internalized, although the rates differed. However, mDC-SIGN was unable to take up FITC-dextran, FITC-ovalbumin, zymosan or heat-killed Candida albicans. The other three lectins showed distinct carbohydrate recognition properties, assessed by blocking FITC-dextran uptake at 37 degrees C and by mannan binding activity at 4 degrees C. Furthermore, only SIGNR1 was efficient in mediating the capture by transfected cells of Gram-negative bacteria, such as Escherichia coli and Salmonella typhimurium, while none of the lectins tested were competent to capture Gram-positive bacteria, Staphylococcus aureus. Interestingly, transfectants with SIGNR1 lacking the cytoplasmic domain were capable of binding FITC-zymosan in a manner that was abolished by EDTA or mannan, but not laminarin. In addition, resident peritoneal CD11b+ cells expressing SIGNR1 bound zymosan at 4 degrees C in concert with a laminarin-sensitive receptor. Therefore these homologous C-type lectins have distinct recognition patters for microbes despite similarities in the carbohydrate recognition domains.
authors.affiliation: Laboratory of Immunobiology, Department of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takahara
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yashima
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Omatsu
authors.forename: Hideo
authors.initials: H
authors.lastname: Yoshida
authors.forename: Yukino
authors.initials: Y
authors.lastname: Kimura
authors.forename: Young-Sun
authors.initials: YS
authors.lastname: Kang
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
authors.forename: Chae Gyu
authors.initials: CG
authors.lastname: Park
authors.forename: Kayo
authors.initials: K
authors.lastname: Inaba
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D000954:Antigens, Surface / Q000235:genetics / Q000502:physiology*; D002176:Candida albicans / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D006224:Cricetinae; D003911:Dextrans / Q000032:analysis; D004926:Escherichia coli / Q000166:cytology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000032:analysis; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics / Q000502:physiology*; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D010587:Phagocytosis / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D012486:Salmonella typhimurium / Q000166:cytology; D014162:Transfection; D015054:Zymosan / Q000032:analysis; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D015054:Zymosan; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C121916:CD207 protein, human; C498497:Cd207 protein, mouse; C494354:SIGNR3 protein, mouse; C015219:fluorescein isothiocyanate dextran