Blocking of the placental immune-modulatory ferritin activates XXXX type cytokines and affects placenta development, fetal growth and the pregnancy outcome.

@entity1 @entity851 @entity59 @entity2047 @entity19 @entity5028 @entity1618 @entity61 @entity777 @entity58 @entity637 @entity630 @entity526
BACKGROUND: @entity5028 ( @entity5028 ) cDNA was recently cloned from the @entity1 placenta, where it is expressed in syncytiotrophoblast and decidual mononuclear cells. @entity5028 and its subcloned bioactive domain (C48), expressed in @entity526 , are immunosuppressive proteins and induce pronounced @entity1618 production in vitro and in vivo. METHODS AND RESULTS: @entity5028 serum level, measured by enzyme-linked immunosorbent assay, was elevated in pregnant @entity19 throughout gestation and declined towards delivery. Blocking of @entity5028 activity by vaccination of @entity19 with C48 prior to mating inhibited pregnancy development. Passive transfer of anti-C48 immunoglobulin (Ig) starting at 3.5-12.5 days post coitum (dpc) resulted in high rate of embryo resorption. Furthermore, treatment with anti-C48 Ig resulted in placental and embryonal growth restriction. At gestation day 13.5, @entity851 was especially notable in the placentae, while at 16.5 dpc it was pronounced in the embryos. Histopathological examination revealed that experimental placentae were globally hypoplastic and the labyrinth was strikingly pale and contained less maternal blood compared with control. Immune-activated spleen cells harvested at 13.5 dpc from anti-C48 Ig-treated pregnant @entity19 secreted in vitro increased level of @entity630 cytokines ( @entity2047 , @entity637 , IL-12) and decreased level of @entity61 cytokines ( @entity1618 , @entity58 , @entity59 , @entity777 ) as compared with the level of the respective cytokines secreted by spleen cells from control pregnant @entity19 . CONCLUSION: This study provides the first in vivo evidence that @entity5028 plays a major role in placentation and embryonic growth.
