Semen Clusterin Is a Novel DC-SIGN Ligand.
Summary of "Semen Clusterin Is a Novel DC-SIGN Ligand."
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.
Affiliation
INSERM U653, Immunité et Cancer, Institut Curie Paris, Paris 75248, France;
Journal Details
This article was published in the following journal.
Name: Journal of immunology (Baltimore, Md. : 1950)
ISSN: 1550-6606
Pages: 5299-309
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22013110
- DOI: http://dx.doi.org/10.4049/jimmunol.1101889
Medical and Biotech [MESH] Definitions
Clusterin
A highly conserved heterodimeric glycoprotein that is differentially expressed during many severe physiological disturbance states such as CANCER; APOPTOSIS; and various NEUROLOGICAL DISORDERS. Clusterin is ubiquitously expressed and appears to function as a secreted MOLECULAR CHAPERONE.
Semen Analysis
The quality of SEMEN, an indicator of male fertility, can be determined by semen volume, pH, sperm concentration (SPERM COUNT), total sperm number, sperm viability, sperm vigor (SPERM MOTILITY), normal sperm morphology, ACROSOME integrity, and the concentration of WHITE BLOOD CELLS.
Aspermia
A condition characterized by the complete absence of SEMEN. This disorder should be differentiated from AZOOSPERMIA, absence of sperm in the semen.
Semen Preservation
The process by which semen is kept viable outside of the organism from which it was derived (i.e., kept from decay by means of a chemical agent, cooling, or a fluid substitute that mimics the natural state within the organism).
Oligospermia
A condition of suboptimal concentration of SPERMATOZOA in the ejaculated SEMEN to ensure successful FERTILIZATION of an OVUM. In humans, oligospermia is defined as a sperm count below 20 million per milliliter semen.
PubMed Articles
Presence, localization, and origin of clusterin in normal human spermatozoa.
PURPOSE: Clusterin in mammalian semen is a secretory form of clusterin (sCLU) with the heterodimeric structure. It is secreted by the epididymis and seminal vesicle. It is generally agreed that cluste...
Evaluation of sperm proteins in infertile men: a proteomic approach.
In this study, the sperm protein profile was compared between fertile and infertile men using 2-dimensional gel electrophoresis, liquid chromatography mass spectrometer analysis, and matrix-assisted l...
The Role of Clusterin in Alzheimer's Disease: Pathways, Pathogenesis, and Therapy.
Genetic variation in clusterin gene, also known as apolipoprotein J, has been associated with Alzheimer's disease (AD) through replicated genome-wide studies, and plasma clusterin levels are associate...
Intravenous clusterin administration reduces myocardial infarct size in rats.
Eur J Clin Invest 2010 Abstract Background Clusterin (Apolipoprotein J), a plasma protein with cytoprotective and complement-inhibiting activities, localizes in the infarcted heart during myocardial i...
BACKGROUND AND AIMS: In vitro studies have shown that clusterin modulates treatment sensitivity in a number of human cancers; however, the interaction between clusterin expression and hypoxia in contr...
Clinical Trials
Concentrations of Maraviroc in the Semen of HIV-Infected Men
The objective of this study is to determine if concentrations of maraviroc in semen exceed the 50% and 95% inhibitory concentrations of HIV during the dose interval. The secondary objecti...
Concentrations of Raltegravir in the Semen of HIV-Infected Men
The objective of this study is to determine if concentrations of raltegravir in semen exceed the 50% and 95% inhibitory concentrations of HIV during the dose interval. The secondary objec...
Pesticides, Industrial Chemicals and Semen Quality
We are conducting an epidemiologic study to investigate the relationship between exposure to pesticides and industrial chemicals and semen quality. We are collecting blood and semen sample...
Semen Analysis After Proton Therapy for Prostate Cancer
The purpose of this study is to evaluate semen for changes following radiation treatment with proton beam radiotherapy alone. The semen samples will be compared for sperm count, sperm move...
Residence Time of Biomarkers of Semen Exposure
The purpose of this study is to examine the vaginal residence time of certain semen biomarkers.
