INTERNALIZATION OF URINARY TRYPSIN-INHIBITOR IN HUMAN UTERINE FIBROBLASTS

We have characterized the molecular species and internalization of uri nary trypsin inhibitor (UTI) in human uterine fibroblasts. Link protei n (LP) has previously been identified as one of the cell-associated UT I binding proteins. The truncated forms of UTI were readily detectable in the cells after incubating the cells with purified UTI. Immunoblot ting analysis with a panel of domain-specific antibodies revealed that the UTI species lacked the amino-terminal domain of UTI, but containe d the carboxyl-terminal domain. We have examined whether LP is involve d in the UTI internalization in the cells. Internalization of I-125-la belled UTI was blocked by the intact UTI, but not by the carboxyl-term inal domain of UTI. Treatment with a polyclonal antibody to the UTI bi nding domain of LP partially inhibited UTI binding to the cells? but d id not significantly prevent UTI internalization. In addition, preincu bation of the cells with hyaluronidase reduced the UTI binding to the cells, but had no effect on the rate with which UTI was internalized. These data allow us to conclude that there are at least two different mechanisms for internalization of UTI. The major one is via unknown UT I receptors in a Ca2+, Mg2+-sensitive manner and another is via LP.