Document Detail


Semen clusterin is a novel DC-SIGN ligand.
MedLine Citation:
PMID:  22013110     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The C-type lectin receptor dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is an important player in the recognition of pathogens by dendritic cells. A plethora of pathogens including viruses, bacteria, parasites, and fungi are recognized by DC-SIGN through both mannose and fucose-containing glycans expressed on the pathogen surface. In this study, we identified semen clusterin as a novel DC-SIGN ligand. Semen clusterin, but not serum clusterin, expresses an extreme abundance of fucose-containing blood-type Ags such as Le(x) and Le(y), which are both excellent DC-SIGN ligands. These motifs enable semen clusterin to bind DC-SIGN with very high affinity (K(d) 76 nM) and abrogate the binding of HIV-1 to DC-SIGN. Depletion of clusterin from semen samples, however, did not completely prevent the ability of semen to inhibit the capture of HIV-1 by DC-SIGN, supporting that besides clusterin, semen contains other DC-SIGN ligands. Further studies are needed to characterize these ligands and define their contribution to the DC-SIGN-blocking activity mediated by semen. Clusterin is an enigmatic protein involved in a variety of physiologic and pathologic processes including inflammation, atherosclerosis, and cancer. Our results uncover an unexpected heterogeneity in the glycosylation pattern of clusterin and suggest that the expression of high concentrations of fucose-containing glycans enables semen clusterin to display a unique set of biological functions that might affect the early course of sexually transmitted infectious diseases.
Authors:
Juan Sabatte; Wolfgang Faigle; Ana Ceballos; Willy Morelle; Christian Rodríguez Rodrígues; Federico Remes Lenicov; Michel Thépaut; Franck Fieschi; Emilio Malchiodi; Marisa Fernández; Fernando Arenzana-Seisdedos; Hugues Lortat-Jacob; Jean-Claude Michalski; Jorge Geffner; Sebastian Amigorena
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-10-17
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  187     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-03     Completed Date:  2012-01-09     Revised Date:  2012-01-26    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5299-309     Citation Subset:  AIM; IM    
Affiliation:
INSERM U653, Immunité et Cancer, Institut Curie Paris, Paris 75248, France.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adult
Antiviral Agents / blood,  metabolism
Cell Adhesion Molecules / blood,  metabolism*
Clusterin / blood,  metabolism*
Dendritic Cells / immunology*,  metabolism*,  virology
Fucose / metabolism
Glycosylation
HIV-1 / immunology,  metabolism
Humans
Lectins, C-Type / blood,  metabolism*
Ligands
Male
Mannose / metabolism
Middle Aged
Protein Binding / immunology
Receptors, Cell Surface / blood,  metabolism*
Recombinant Proteins / blood,  metabolism
Semen / immunology*,  metabolism*,  virology
Chemical
Reg. No./Substance:
0/Antiviral Agents; 0/Cell Adhesion Molecules; 0/Clusterin; 0/DC-specific ICAM-3 grabbing nonintegrin; 0/Lectins, C-Type; 0/Ligands; 0/Receptors, Cell Surface; 0/Recombinant Proteins; 31103-86-3/Mannose; 3713-31-3/Fucose

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  CBG Santiago: a Novel CBG Mutation.
Next Document:  The Role of Neutral Endopeptidase in Caerulein-Induced Acute Pancreatitis.