Why is erythropoietin present in human milk? Studies of erythropoietin receptors on enterocytes of human and rat neonates

Erythropoietin receptors (Epo-R) are expressed on cells in the small bowel of human fetuses, but their function has not been defined. We hypothesized that intestinal Epo-R are present post natally, and that recombinant erythr opoietin (rEpo) would increase enterocyte migration and decrease cytokine-i nduced apoptosis. We used reverse transcriplase-polymerase chain reaction a nd immunohistochemistry to evaluate the presence of Epo-R mRNA and protein in rat intestinal epithelial cells (IEC-6), and in postnatal human and rat bowel. The effect of rEpo on rates of cell migration and proliferation were established in IEC-6 cells by using cell counting and incorporation of bro modeoxyuridine. To determine whether rEpo affects response to injury, cells were pretreated with rEpo, then were damaged with 25 or 50 ng/mL tumor nec rosis factor-cu plus 2.5 mu g/mL cycloheximide. Cell death was determined b y colorimetric bioassay. We found that Epo-R mRNA and protein were expresse d by IEC-6 cells and by enterocytes of postnatal rat and human small bowel. Cells that had been exposed to 0.05 or 5.00 U/mL rEpo migrated faster than did the controls ip ( 0.05), but no difference was noted in cell prolifera tion. Treatment of IEC-6 cells with rEpo before or at the time of injury re sulted in a lower percentage of cell death, and this effect was neutralized by anti-Epo antibody. We conclude that Epo-R is expressed in enterocytes p ostnatally in rats and humans. Recombinant Epo increases the rate of migrat ion of IEC-6 cells and decreases cytokine-induced apoptosis. These studies suggest that Epo within human milk has actions on neonate's intestinal func tion.