Suppression by Human Placental Protein 14 of Natural Killer Cell Activity

Abstract

Human decidua of early pregnancy contains considerable numbers of CD3-CD56+ natural killer (NK) cells. In this study, two major protein products of the decidua, placental protein 14 (PP14) and placental protein 12 (PP12), were tested for the ability to regulate human NK cell activity. In vitro overnight exposure to PP14 of blood lymphocytes or purified large granular lymphocytes (LGL) resulted in suppression of cytotoxicity against K562 target cells in a 4-h 51Cr release assay. The NK inhibition was dependent on concentrations of PP14, being detectable at 5 micrograms/ml and reaching maximum at 50 micrograms/ml. Manifestation of PP14-induced NK suppression required 18-h contact with NK cells. The suppression of NK activity by PP14 was not abolished by indomethacin. In a target binding assay the number of PP14-treated LGL binding to K562 was comparable to that of untreated ones. By contrast with PP14, PP12 produced no effects on NK cells. These results indicate that PP14 suppresses the function of NK cells, which might be involved in prevention of maternal immune rejection of fetus at the fetomaternal interface.

Angiogenic role for glycodelin in tumorigenesis

“…Our results indicate that Gp can induce VEGF expression in some cell lines and VEGF receptor Flt-1 in HUVECs. Glycodelin usually has been considered to play an immunosuppressive function in embryo implantation and tumor development (18,19). Our results suggest that glycodelin also might play an important role in embryogenesis and tumor development by inducing angiogenesis.…”

“…A potential role for glycodelin in embryonic implantation has been confirmed as facilitating evasion of the maternal immune response (17)(18)(19). The biological function of glycodelin in tumor has not been clarified yet.…”

“…Serum levels of glycodelin are elevated in the late secretory phase and in the first trimester of pregnancy (16). The physiological role of glycodelin is not well known, but in vitro studies have shown that it can inhibit natural killer cell activity (17)(18)(19). Elevated levels of glycodelin also are seen in the plasma of patients with ovarian and uterine malignancies (20).…”

The lipocalin protein family: structure and function

“…Recently, Morrow et al have shown that PP14 is expressed by haematopoietic cells of the megakaryocytic lineage and demonstrates potent immunosuppressive properties which can be blocked by PP14-specific antibodies [92]. PP14 has also been reported to suppress the activity of natural killer cells and T-cells [93]. Seppala et al recently reviewed other immunoregulatory properties of PP14 [94].…”

Placental Protein 14 Induces Apoptosis in T Cells but Not in Monocytes

“…Apart from this, PP14 has been shown to have immunosuppressive properties in that it inhibits both phytohemagglutinin (14) and anti-CD3 antibody-induced lymphocyte proliferation (15). PP14 also inhibits Natural Killer cell activity (16). That the protein is essential for normal pregnancy progression has been established by the association of low levels of PP14 with habitual abortion (17,18), unexplained infertility (19), and establishment of pregnancy in women during those cycles in which normal concentrations of PP14 were detected (20).…”