Pregnancy zone protein is a carrier and modulator of placental protein-14 in T-cell growth and cytokine production.
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.[1]References
- Pregnancy zone protein is a carrier and modulator of placental protein-14 in T-cell growth and cytokine production. Skornicka, E.L., Kiyatkina, N., Weber, M.C., Tykocinski, M.L., Koo, P.H. Cell. Immunol. (2004) [Pubmed]
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