MACROPHAGE-COLONY-STIMULATING FACTOR (M-CSF) REGULATES THE EXPRESSIONOF FIBRONECTIN AND ITS ALPHA-5 INTEGRIN RECEPTOR IN HUMAN TROPHOBLASTS

Macrophage-colony stimulating factor (M-CSF, CSF-I) is secreted by hum an trophoblasts as well as endometrial cells, while its receptor c-fms is abundantly expressed by the extravillous trophoblasts anchoring th e placenta to the uterus, suggesting a role for M-CSF at the maternal- fetal interface. We investigated the effect of M-CSF an the expression of fibronectin and its receptor, the alpha(5) integrin, in human trop hoblasts. Exposure of trophoblasts to M-CSF produced a two to three-fo ld increase in fibronectin and alpha(5) mRNA abundance at both 24 and 72 hours of culture. A dose-dependent increase in cellular fibronectin secretion into the culture medium was detected at both time points. I mmunocytochemistry showed co-focalization of cellular fibronectin and alpha(5) in the cells, suggesting that attachment of trophoblasts to f ibronectin is mediated in part by the alpha(5) beta(1) integrin. We co nclude that M-CSF increases fibronectin expression and secretion by th e human trophoblasts, and up-regulates its specific receptor, the alph a(5) integrin. We hypothesize that M-CSF may partake in the autocrine/ paracrine mechanisms regulating trophoblast invasion during implantati on.