title: Pregnancy zone protein is a carrier and modulator of placental protein-14 in T-cell growth and cytokine production.
abstract: A successful pregnancy can only occur when the maternal immune system fails to attack the allogeneic fetus. Two plasma proteins with described immunoregulatory activities, pregnancy zone protein (PZP) and placental protein-14 (PP14; also known as glycodelin-A), increase dramatically during pregnancy, prompting us to examine their potential role in mediating fetal protection. First, we demonstrated that both native PZP and its receptor-recognized monoamine-activated form (MA-PZP) bound non-covalently and specifically to PP14, exhibiting K(d) values greater than 3 microM, as determined by surface plasmon resonance. Our evidence further suggests that PZP is potentially a more effective carrier of PP14 than its relative alpha2-macroglobulin. Second, we found that T-cell activation, as measured by increased proliferation and IL-2 production, was inhibited by either PZP or PP14 in a dose-dependent manner. However, when PZP and PP14 were combined, they acted synergistically to inhibit T cell proliferation and IL-2 production. Interestingly, the combination of PZP and PP14 had little effect on the production of T(H)2 cytokine, IL-4. Based upon these findings, we hypothesize that PZP and PP14 form a stable complex in the plasma of pregnant women and together act synergistically to selectively modulate T-cell activation. Mechanistically, this activity appears to be independent of the PZP receptor (CD91) or PZP's anti-proteinase activity.
authors.affiliation: Department of Microbiology and Immunology, Northeastern Ohio Universities College of Medicine, P.O. Box 95, Rootstown, OH 44272, USA.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Skornicka
authors.forename: Nadya
authors.initials: N
authors.lastname: Kiyatkina
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Weber
authors.forename: Mark L
authors.initials: ML
authors.lastname: Tykocinski
authors.forename: Peter H
authors.initials: PH
authors.lastname: Koo
mesh_terms: D015703:Antigens, CD / Q000187:drug effects / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D005260:Female; D000071816:Glycodelin; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008213:Lymphocyte Activation / Q000276:immunology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D000511:alpha-Macroglobulins / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D002352:Carrier Proteins; D016207:Cytokines; D000071816:Glycodelin; D006023:Glycoproteins; D007376:Interleukin-2; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C045246:PAEP protein, human; C472887:PZP protein, human; D011257:Pregnancy Proteins; D000511:alpha-Macroglobulins; D015847:Interleukin-4