The effect of ceruloplasmin on iron release from placental (BeWo) cells: Evidence for an endogenous Cu oxidase

The mechanism of iron release from the placenta into the fetal circulation is not well understood. Ceruloplasmin, a plasma ferroxidase, has been impli cated in iron efflux from a variety of cell types. The hypothesis is that c irculating ceruloplasmin facilitates iron efflux by oxidizing the released Fe(II) to Fe(III) for incorporation into transferrin. We tested whether thi s mechanism mediates iron release from placental cells into the fetal circu lation, using the BeWo cell fine, a choriocarcinoma which can differentiate into a syncytium. Fe-59 release from undifferentiated or differentiated ce lls and from cells grown on porous filters was not stimulated by extracellu lar ceruloplasmin. Instead, we found that BeWo cells express an endogenous ferroxidase. The protein is membrane bound and cross-reacts with an anti-ce ruloplasmin antibody, but has a different size; 100 and 140 kDa. Similar im munoreactivity was identified in first- and third-trimester human placentae . In BeWo cells, the protein has a perinuclear localization but does not en tirely co-localize with markers for the endoplasmic reticulum or Golgi appa ratus. We propose that this oxidase performs the same function as serum cer uloplasmin and is involved in iron release into the fetal circulation. (C) 2000 Harcourt Publishers Ltd.