title: Human pregnancy-specific glycoprotein 1a (PSG1a) induces alternative activation in human and mouse monocytes and suppresses the accessory cell-dependent T cell proliferation.
abstract: It has been proposed that pregnancy-specific factors induce the suppression of a specific arm of the maternal response accompanied by activation of the nonspecific, innate immune system. The aim of this study was to determine whether pregnancy-specific glycoprotein 1a (PSG1a), the major variant of PSG polypeptides, is able to modulate the monocyte/macrophage (Mo) metabolism to regulate T cell activation and proliferation. Using the recombinant form of this glycoprotein (rec-PSG1a), expressed in mammalian cells with a vaccinia-based expression vector, we have demonstrated that human PSG1a induces arginase activity in peripheral blood human Mo and human and murine Mo cell lines. In addition, rec-PSG1a is able to induce alternative activation because it up-regulates the arginase activity and inhibits the nitric oxide production in Mo activated by lipopolysaccharides. We also observed that rec-PSG1a is an important accessory cells-dependent T cell suppressor factor that causes partial growth arrest at the S/G2/M phase of the cell cycle. Additionally, an impaired T cell proliferative response induced by mitogens and specific antigen was observed in BALB/c mice upon in vivo expression of PSG1a. Our results suggest that PSG1a function contributes to the immunomodulation during pregnancy, having opposite effects on maternal innate and adaptative systems.
authors.affiliation: Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina. cmotran@bioclin.fcq.unc.edu.ar
authors.forename: Claudia Cristina
authors.initials: CC
authors.lastname: Motrán
authors.forename: Fernando López
authors.initials: FL
authors.lastname: Díaz
authors.forename: Adriana
authors.initials: A
authors.lastname: Gruppi
authors.forename: Daniela
authors.initials: D
authors.lastname: Slavin
authors.forename: Bruno
authors.initials: B
authors.lastname: Chatton
authors.forename: José Luis
authors.initials: JL
authors.lastname: Bocco
mesh_terms: D000818:Animals; D001119:Arginase / Q000096:biosynthesis / Q000235:genetics; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006031:Glycosylation; D006367:HeLa Cells / Q000166:cytology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000502:physiology*; D007959:Lymphocyte Culture Test, Mixed; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000166:cytology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011247:Pregnancy / Q000276:immunology*; D011268:Pregnancy-Specific beta 1-Glycoproteins / Q000235:genetics / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D008070:Lipopolysaccharides; D011268:Pregnancy-Specific beta 1-Glycoproteins; D011993:Recombinant Fusion Proteins; D003208:Concanavalin A; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D001119:Arginase