Iron saturation alters the effect of lactoferrin on the proliferation and differentiation of human enterocytes (Caco-2 cells).
Recent studies have indicated that lactoferrin may act as a cell mitogen. The effect of human and bovine lactoferrins on the proliferation and differentiation of a human intestinal epithelial cell line (Caco-2) was investigated and compared with that of human transferrin. Caco-2 cells were cultured in serum-free media supplemented with both iron-unsaturated and -saturated forms of the iron-binding proteins. Cell proliferation and differentiation were evaluated by examining growth curves and measuring sucrase and alkaline phosphatase activities of brush border membrane fractions, respectively. The iron-binding status of lactoferrins and transferrin affected the proliferation of Caco-2 cells. The iron-saturated forms of human (S-hLf), bovine (S-bLf) lactoferrins and human transferrin (S-hTf) enhanced cell proliferation, while iron-unsaturated forms (U-hLf, U-bLf, and U-hTf) suppressed it. Iron-binding status also determined the effect of lactoferrin and transferrin on cellular differentiation, but this effect differed for different brush border enzymes. S-hTf enhanced sucrase activity more than S-hLF or S-bLf. Both U-hLf and U-bLf markedly suppressed sucrase activity. U-hTf suppressed alkaline phosphatase activity appreciably, while the other iron-binding proteins showed no significant effect on it. Lactoferrin and transferrin may modulate the proliferation and differentiation of intestinal epithelial cells, but their efficacy depends on their saturation with iron.
Oguchi
S
S
Developmental Gastroenterology Laboratory, Massachusetts General Hospital, Boston 02129-2060, USA.
Walker
W A
WA
Sanderson
I R
IR
D000818:Animals; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003470:Culture Media; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D006801:Humans; D007422:Intestines / Q000166:cytology* / Q000187:drug effects; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D007781:Lactoferrin / Q000378:metabolism / Q000494:pharmacology*; D013393:Sucrase / Q000378:metabolism; D014168:Transferrin / Q000494:pharmacology
D003470:Culture Media; D014168:Transferrin; D007501:Iron; D013393:Sucrase; D007781:Lactoferrin