Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Expression of Fas but not Fas ligand on fetal pig β cells

Expression of Fas but not Fas ligand on fetal pig β cells Abstract: Background: The aim of this study was to determine whether fetal pig insulin‐producing cells, a potential source of transplantable tissue for the treatment of type 1 diabetes, are affected by the Fas–FasL interaction, one of the cytotoxic pathways involved in T‐cell‐mediated autoimmune destruction of pancreatic β cells. Methods: Expression of Fas/FasL on fetal pig β cells was assessed by immunohistochemistry, flow cytometry, Western blot, and RT‐PCR. Apoptosis of fetal pig β cells induced by soluble FasL (sFasL) or anti‐Fas antibody (APO‐1) was detected by flow cytometry using PI. Expression of FLIP on fetal pig pancreatic tissue was detected by immunofluorescent staining and Western blot. Results: Fas was expressed on fetal pig pancreatic cells, both β and non‐β cells, and the level of expression could be upregulated by exposure to human interleukin‐1β (IL1β) 2000 pg/ml for 24 h. In contrast, FasL was not detected on fetal pig pancreatic cells but could be induced on both β and non‐β cells when the cells were treated with IL1β. Fas persisted on fetal pig β cells transplanted as islet‐like cell clusters into severe combined immunodeficient mice, with expression of this antigen at all times examined, 1 day, 2, 3 and 4 weeks. FasL was absent. Despite the presence of Fas on fetal pig β cells, addition of sFasL or anti‐Fas antibody failed to induce apoptosis of the fetal pig β cells. In contrast, pig lymphocytes, which express Fas, were destroyed by addition of both sFasL and APO‐1. A possible reason for this is the expression on the fetal pig pancreatic cells of FLIP, an inhibitor of Fas‐induced apoptosis. Conclusions: Fetal pig β cells are resistant to Fas–FasL destruction. Our data imply that fetal pig β cells transplanted into humans with type 1 diabetes may not be destroyed by activated T cells through the Fas–FasL‐mediated pathway. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Xenotransplantation Wiley

Expression of Fas but not Fas ligand on fetal pig β cells

Download PDF
10 pages

Loading next page...
 
/lp/wiley/expression-of-fas-but-not-fas-ligand-on-fetal-pig-cells-IhR7gA6NIC

References (38)

Publisher
Wiley
Copyright
Copyright © 2004 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0908-665X
eISSN
1399-3089
DOI
10.1111/j.1399-3089.2004.00158.x
pmid
15303979
Publisher site
See Article on Publisher Site

Abstract

Abstract: Background: The aim of this study was to determine whether fetal pig insulin‐producing cells, a potential source of transplantable tissue for the treatment of type 1 diabetes, are affected by the Fas–FasL interaction, one of the cytotoxic pathways involved in T‐cell‐mediated autoimmune destruction of pancreatic β cells. Methods: Expression of Fas/FasL on fetal pig β cells was assessed by immunohistochemistry, flow cytometry, Western blot, and RT‐PCR. Apoptosis of fetal pig β cells induced by soluble FasL (sFasL) or anti‐Fas antibody (APO‐1) was detected by flow cytometry using PI. Expression of FLIP on fetal pig pancreatic tissue was detected by immunofluorescent staining and Western blot. Results: Fas was expressed on fetal pig pancreatic cells, both β and non‐β cells, and the level of expression could be upregulated by exposure to human interleukin‐1β (IL1β) 2000 pg/ml for 24 h. In contrast, FasL was not detected on fetal pig pancreatic cells but could be induced on both β and non‐β cells when the cells were treated with IL1β. Fas persisted on fetal pig β cells transplanted as islet‐like cell clusters into severe combined immunodeficient mice, with expression of this antigen at all times examined, 1 day, 2, 3 and 4 weeks. FasL was absent. Despite the presence of Fas on fetal pig β cells, addition of sFasL or anti‐Fas antibody failed to induce apoptosis of the fetal pig β cells. In contrast, pig lymphocytes, which express Fas, were destroyed by addition of both sFasL and APO‐1. A possible reason for this is the expression on the fetal pig pancreatic cells of FLIP, an inhibitor of Fas‐induced apoptosis. Conclusions: Fetal pig β cells are resistant to Fas–FasL destruction. Our data imply that fetal pig β cells transplanted into humans with type 1 diabetes may not be destroyed by activated T cells through the Fas–FasL‐mediated pathway.

Journal

Xenotransplantation – Wiley

Published: Sep 1, 2004

There are no references for this article.