Increased fas antigen in uremia accelerates adhesion of mononuclear cells to endothelial and sinovial cells via stimulated hyaluronan production

We examined influences of increased soluble Fas (sFas) and hyaluronan in ur emia on apoptosis and peripheral blood mononuclear cell (MNC) adhesiveness. Synovocytes, human umbilical cord endothelial cells (HUVEC), human coronar y artery smooth muscle cells (CASMC), and MNC were prepared in this study. In cultures of synovocytes, HUVEC, and CASMC, sFas or high molecular hyalur onan was added to media at medium change. After 1 day, Fas-positive cells w ere calculated by fluorescence-activated cell sorting. Uremic level of sFas enhanced Fas-positive cells in all cell lines (P < 0.01) not in CASMC. On the contrary, hyaluronan inhibited Fas expression in all cell lines (P < 0. 05). In culture with uremic serum, Fas were induced in all cell lines. At t his time, the hyaluronan levels of the supernatant were measured and hyalur onan production was estimated. In contrast to the results using sFas supple ment, hyaluronan production was increased in culture with sFas and uremic s era. MNC adhesiveness was increased in synovocytes and HUVEC lines by addin g hyaluronan or sFas. Higher adherent cell numbers were recognized when bot h sFas and hyaluronan were added to the media. A most remarkable increase i n cell numbers was observed In uremic MNC suspension as compared with that of MNC from healthy subjects. In conclusion, these results Indicate that In creased sFas in uremia stimulates apoptosis and hyaluronan production. Both sFas and hyaluronan are responsible for accelerated MNC adhesiveness in ur emia. (C) 2001 by the National Kidney Foundation, Inc.