Human pregnancy-specific glycoprotein 1a (PSG1a) induces alternative activation in human and mouse monocytes and suppresses the accessory cell-dependent T cell proliferation.
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.
Motrán
Claudia Cristina
CC
Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina. cmotran@bioclin.fcq.unc.edu.ar
Díaz
Fernando López
FL
Gruppi
Adriana
A
Slavin
Daniela
D
Chatton
Bruno
B
Bocco
José Luis
JL
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*
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