PMID- 26976925
OWN - NLM
STAT- MEDLINE
DCOM- 20170515
LR  - 20231111
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 473
IP  - 10
DP  - 2016 May 15
TI  - Human DC-SIGN binds specific human milk glycans.
PG  - 1343-53
LID - 10.1042/BCJ20160046 [doi]
AB  - Human milk glycans (HMGs) are prebiotics, pathogen receptor decoys and regulators 
      of host physiology and immune responses. Mechanistically, human lectins 
      (glycan-binding proteins, hGBP) expressed by dendritic cells (DCs) are of major 
      interest, as these cells directly contact HMGs. To explore such interactions, we 
      screened many C-type lectins and sialic acid-binding immunoglobulin-like lectins 
      (Siglecs) expressed by DCs for glycan binding on microarrays presenting over 200 
      HMGs. Unexpectedly, DC-specific intercellular adhesion molecule-3-grabbing 
      non-integrin (DC-SIGN) showed robust binding to many HMGs, whereas other C-type 
      lectins failed to bind, and Siglec-5 and Siglec-9 showed weak binding to a few 
      glycans. By contrast, most hGBP bound to multiple glycans on other microarrays 
      lacking HMGs. An alpha-linked fucose residue was characteristic of HMGs bound by 
      DC-SIGN. Binding of DC-SIGN to the simple HMGs 2'-fucosyl-lactose (2'-FL) and 
      3-fucosyl-lactose (3-FL) was confirmed by flow cytometry to beads conjugated with 
      2'-FL or 3-FL, as well as the ability of the free glycans to inhibit DC-SIGN 
      binding. 2'-FL had an IC50 of  approximately 1 mM for DC-SIGN, which is within the 
      physiological concentration of 2'-FL in human milk. These results demonstrate 
      that DC-SIGN among the many hGBP expressed by DCs binds to alpha-fucosylated HMGs, 
      and suggest that such interactions may be important in influencing immune 
      responses in the developing infant.
CI  - (c) 2016 The Author(s). published by Portland Press Limited on behalf of the 
      Biochemical Society.
FAU - Noll, Alexander J
AU  - Noll AJ
AD  - The Glycomics Center, Department of Biochemistry, Emory University School of 
      Medicine, Atlanta, GA 30322, U.S.A. Program in Microbiology and Molecular 
      Genetics, Graduate Division of Biological and Biomedical Sciences, Laney Graduate 
      School, Emory University, Atlanta, GA 30322, U.S.A.
FAU - Yu, Ying
AU  - Yu Y
AD  - The Glycomics Center, Department of Biochemistry, Emory University School of 
      Medicine, Atlanta, GA 30322, U.S.A.
FAU - Lasanajak, Yi
AU  - Lasanajak Y
AD  - The Glycomics Center, Department of Biochemistry, Emory University School of 
      Medicine, Atlanta, GA 30322, U.S.A.
FAU - Duska-McEwen, Geralyn
AU  - Duska-McEwen G
AD  - Abbott Nutrition, Global Discovery R&D, Columbus, OH 43215, U.S.A.
FAU - Buck, Rachael H
AU  - Buck RH
AD  - Abbott Nutrition, Global Discovery R&D, Columbus, OH 43215, U.S.A.
FAU - Smith, David F
AU  - Smith DF
AD  - The Glycomics Center, Department of Biochemistry, Emory University School of 
      Medicine, Atlanta, GA 30322, U.S.A.
FAU - Cummings, Richard D
AU  - Cummings RD
AD  - The Glycomics Center, Department of Biochemistry, Emory University School of 
      Medicine, Atlanta, GA 30322, U.S.A. rcummin1@bidmc.harvard.edu.
LA  - eng
GR  - P41 GM103694/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160314
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (DC-specific ICAM-3 grabbing nonintegrin)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Polysaccharides)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Sialic Acid Binding Immunoglobulin-like Lectins)
RN  - 0 (Trisaccharides)
RN  - XO2533XO8R (2'-fucosyllactose)
SB  - IM
MH  - Cell Adhesion Molecules/*metabolism
MH  - Dendritic Cells/metabolism
MH  - Humans
MH  - Lectins, C-Type/*metabolism
MH  - Milk, Human/*chemistry
MH  - Polysaccharides/*metabolism
MH  - Protein Array Analysis
MH  - Protein Binding
MH  - Receptors, Cell Surface/*metabolism
MH  - Sialic Acid Binding Immunoglobulin-like Lectins/metabolism
MH  - Trisaccharides/metabolism
PMC - PMC4875834
MID - NIHMS782578
OTO - NOTNLM
OT  - dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin 
      (DC-SIGN)
OT  - glycan microarrays
OT  - glycan recognition
OT  - glycan-binding proteins
OT  - human milk glycans
OT  - lectins
COIS- Declarations of Interest R.D.C. and D.F.S. are consultants for Abbott Nutrition. 
      G.D.M. and R.H.B. are employees of Abbott. The other authors declare that they 
      have no conflict of interest in the work reported.
EDAT- 2016/03/16 06:00
MHDA- 2017/05/16 06:00
PMCR- 2016/05/22
CRDT- 2016/03/16 06:00
PHST- 2016/02/01 00:00 [received]
PHST- 2016/03/14 00:00 [accepted]
PHST- 2016/03/16 06:00 [entrez]
PHST- 2016/03/16 06:00 [pubmed]
PHST- 2017/05/16 06:00 [medline]
PHST- 2016/05/22 00:00 [pmc-release]
AID - BCJ20160046 [pii]
AID - 10.1042/BCJ20160046 [doi]
PST - ppublish
SO  - Biochem J. 2016 May 15;473(10):1343-53. doi: 10.1042/BCJ20160046. Epub 2016 Mar 
      14.