Expression of functionally active FcRn and the differentiated bidirectional transport of IgG in human placental endothelial cells

The mechanism of selective transport of the immunoglobulins G from the plac ental struma to che lumen of the fetal blood vessels has not been elucidate d yet. It was postulated that the specific transport as well as the regulat ion of IgG level ill the blood, involves the MHC class I related receptor F cRn for the Fc domain of IgG. We questioned whether human placental endothe lial cells (HPEC) express FcRn and, if present, whether it is in a function ally active form. The experiments were performed on cultured HPEC and as po sitive control, human trophoblastic (JEG3) and mouse endothelial cells (SVE C) were used. Expression of FcRn, was demonstrated by indirect immunofluore scence and RT-PCR. The role of FcRn was assessed by quantifying the transce llular transport of [I-125]-hIgG or [I-125)-rF(ab')(2) fragments from the a pical to basolateral surface, and in the reverse direction of HPEC grown on filters in a double chamber system. The intracellular pathway of FcRn or I gG was examined by electron microscopy using the proteins adsorbed to 5 nm and 20 nm colloidal Sold particles, respectively. The results showed that: (a) FcRn is expressed by human placental endothelial cells, in a functional ly active form; ib) transcytosis of IgG in HPEC is a rime-dependent process that cakes place preferentially from the basolateral to the apical compart ment; and (c) both IgG and FcRn colocalize in an intracellular endocytic co mpartment, chloroquine sensitive. Together these data suggest that the regu lation of IgG level by endothelial cells may result from interplay between salvaging, exocytosis, and transcytosis of the molecules. One can assume th at IgG that does not bind to FcRn may be destined For destruction, and this would explain the mechanism by which IgG homeostasis is maintained. (C) Am erican Society for Histocompatibility and Immunogenetics, 2001. Published b y Elsevier Science Inc.