title: Tumor biomarker glycoproteins in the seminal plasma of healthy human males are endogenous ligands for DC-SIGN.
abstract: DC-SIGN is an immune C-type lectin that is expressed on both immature and mature dendritic cells associated with peripheral and lymphoid tissues in humans. It is a pattern recognition receptor that binds to several pathogens including HIV-1, Ebola virus, Mycobacterium tuberculosis, Candida albicans, Helicobacter pylori, and Schistosoma mansoni. Evidence is now mounting that DC-SIGN also recognizes endogenous glycoproteins, and that such interactions play a major role in maintaining immune homeostasis in humans and mice. Autoantigens (neoantigens) are produced for the first time in the human testes and other organs of the male urogenital tract under androgenic stimulus during puberty. Such antigens trigger autoimmune orchitis if the immune response is not tightly regulated within this system. Endogenous ligands for DC-SIGN could play a role in modulating such responses. Human seminal plasma glycoproteins express a high level of terminal Lewis(x) and Lewis(y) carbohydrate antigens. These epitopes react specifically with the lectin domains of DC-SIGN. However, because the expression of these sequences is necessary but not sufficient for interaction with DC-SIGN, this study was undertaken to determine if any seminal plasma glycoproteins are also endogenous ligands for DC-SIGN. Glycoproteins bearing terminal Lewis(x) and Lewis(y) sequences were initially isolated by lectin affinity chromatography. Protein sequencing established that three tumor biomarker glycoproteins (clusterin, galectin-3 binding glycoprotein, prostatic acid phosphatase) and protein C inhibitor were purified by using this affinity method. The binding of DC-SIGN to these seminal plasma glycoproteins was demonstrated in both Western blot and immunoprecipitation studies. These findings have confirmed that human seminal plasma contains endogenous glycoprotein ligands for DC-SIGN that could play a role in maintaining immune homeostasis both in the male urogenital tract and the vagina after coitus.
authors: Division of Reproductive and Perinatal Research, Department of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, Missouri 65211. Electronic address: clarkgf@health.missouri.edu.
authors: Gary F
authors: GF
authors: Clark
authors: Division of Molecular Biosciences, Faculty of Natural Sciences, Imperial College London, SW7 2AZ, United Kingdom.
authors: Paola
authors: P
authors: Grassi
authors: Division of Molecular Biosciences, Faculty of Natural Sciences, Imperial College London, SW7 2AZ, United Kingdom.
authors: Poh-Choo
authors: PC
authors: Pang
authors: Division of Molecular Biosciences, Faculty of Natural Sciences, Imperial College London, SW7 2AZ, United Kingdom.
authors: Maria
authors: M
authors: Panico
authors: Division of Reproductive and Perinatal Research, Department of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, Missouri 65211.
authors: David
authors: D
authors: Lafrenz
authors: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Women's Health, University of Missouri, Columbia, Missouri 65211.
authors: Erma Z
authors: EZ
authors: Drobnis
authors: Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, Missouri 65211.
authors: Michael R
authors: MR
authors: Baldwin
authors: Division of Molecular Biosciences, Faculty of Natural Sciences, Imperial College London, SW7 2AZ, United Kingdom.
authors: Howard R
authors: HR
authors: Morris
authors: Division of Molecular Biosciences, Faculty of Natural Sciences, Imperial College London, SW7 2AZ, United Kingdom.
authors: Stuart M
authors: SM
authors: Haslam
authors: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors: Sophia
authors: S
authors: Schedin-Weiss
authors: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors: Wei
authors: W
authors: Sun
authors: Division of Molecular Biosciences, Faculty of Natural Sciences, Imperial College London, SW7 2AZ, United Kingdom.
authors: Anne
authors: A
authors: Dell
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008024:Ligands; D008297:Male; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012661:Semen / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D037181:Lectins, C-Type; D008024:Ligands; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin