The neonatal IgG receptor FcRn, is expressed in the human fetal intestine and the non-malignant fetal intestinal epithelial cell line

Abstract

The neonatal Fc receptor FcRn functions in rodents to transfer maternal gammaglobulins (IgG) from mother to young via the neonatal intestine. In humans most of this transfer is presumed to occur in utero via the placenta. The fetus swallows amniotic fluid that contains immunogiobulins but it is unknown whether this transfer also occurs via the fetal intestine. Human FcRn has been identified in the human syncitiotrophoblast and plays a role in the materno-fetal transfer of antibody. It is also expressed in adult intestine and may be important in IgG catabolism. Objective: We hypothesize that the FcRn receptor is expressed in the human fetal intestine and may play a role in IgG transport from the amniotic fluid/colostrum into the fetal circulation. We wish to demonstrate expression of the FcRn 1) along different segments of the human fetal intestine and 2) in a human non-malignant fetal intestinal epithelial cell line (H4). Methods: Lysates were prepared from human fetal stomach, small intestine and colon from a 22 week gestation fetus and from H4 cells. Caco-2 cells and T-84 cells were used as positive controls. Prepared lysates were run on Western blots and were probed with anti-FcRn antibodies. Bound antibody was detected by HRP-conjugated secondary antibody and enhanced chemiluminescence. FcRn expression was normalized against GAPDH and quantitated by densitometry. Immunostaining of human fetal intestine, neonatal mouse intestine (+ contro[), H4 cells and T-B4 ceils (+ control), was done with a rabbit anti-human FcRn antibody and detected with the appropriate conjugated secondary antibody for microscopy. Results: The FcRn heavy chain was detected from the fetal intestine and H4 cells on Western blot analysis. On immunostaining, a subapical staining pattern for FcRn was seen on human fetal intestine. The H4 cells also stained positive for FcRn. Conclusion: FcRn expression is demonstrated in the human fetal intestine and in the human non-malignant fetal intestinal epithelial cell line (H4) suggesting that FcRn may play a role in the uptake and transport of IgG in the fetus.