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 uremia on apoptosis and peripheral blood mononuclear cell (MNC) adhesiveness. Synovocytes, human umbilical cord endothelial cells (HUVEC), human coronary artery smooth muscle cells (CASMC), and MNC were prepared in this study. In cultures of synovocytes, HUVEC, and CASMC, sFas or high molecular hyaluronan was added to media at medium change. After 1 day, Fas-positive cells were 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 this time, the hyaluronan levels of the supernatant were measured and hyaluronan production was estimated. In contrast to the results using sFas supplement, hyaluronan production was increased in culture with sFas and uremic sera. MNC adhesiveness was increased in synovocytes and HUVEC lines by adding hyaluronan or sFas. Higher adherent cell numbers were recognized when both sFas and hyaluronan were added to the media. A most remarkable increase in cell numbers was observed in uremic MNC suspension as compared with that of MNC from healthy subjects. In conclusion, these results indicate that increased sFas in uremia stimulates apoptosis and hyaluronan production. Both sFas and hyaluronan are responsible for accelerated MNC adhesiveness in uremia.
Matsumoto
J
J
4th Department of Internal Medicine, Teikyo University School of Medicine, Kawasaki City, Kanagawa, Japan. yonnai@med.teikyo-u.ac.jp
Yanagisawa
N
N
Konoma
T
T
Haizuka
H
H
Nakashima
Y
Y
Sato
M
M
D000268:Adhesiveness; D017209:Apoptosis; D002448:Cell Adhesion; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D006435:Renal Dialysis; D013583:Synovial Membrane / Q000378:metabolism*; D014511:Uremia / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
D019014:fas Receptor; D006820:Hyaluronic Acid