Localization of hepatocyte growth factor activator inhibitor type 1 in Langhans' cells of human placenta

Activation of hepatocyte growth factor (HGF) is a crucial limiting step in HGF-induced signaling pathway. The HGF activator inhibitor type I (HAI-I) w as identified as a potent inhibitor of HGF activator (HGFA), a serine prote inase that is responsible for the activation of HGF in vivo. HAI-1 is an in tegral membrane Kunitz-type serine proteinase inhibitor, and its mRNA has b een reported to be most abundant in the placenta. In this report, specific antibody to HAI-1 was used in an immunohistochemical procedure to determine the localization of HAI-1 in human placenta. HAI-I was expressed in cytotr ophoblasts (Langhans' cells) of the double-layered trophoblastic epithelium of chorionic villi tissue, and syncytiotrophoblasts were almost negative. On the other hand, extravillous trophoblasts of cytotrophoblastic columns s howed markedly decreased immunoreactivity, and those infiltrating into the superficial decidua membrane of early placenta were hardly stainable. The a mnionic epithelial cells were also immunostained intensely. The presence of HAI-1 mRNA was also confirmed in a cultured human cytotrophoblastic cell l ine. In addition to HAI-I, low but distinct expression of HGFA mRNA was obs erved in the placenta tissue and cultured cytotrophoblasts by using a sensi tive RT-PCR method. Since HGF plays an essential role in the placenta devel opment, expression of HAI-I and HGFA may have an important regulatory role in the placenta. The localization of HAI-1 in the proliferating trophoblast ic stem cells (Langhans' cells), but not in syncytiotrophoblasts and extrav illous trophoblasts, suggest a possible role of HAI-1 in the proliferation of trophoblasts.