Cytotoxicity of peritoneal murine macrophages against encapsulated pancreatic rat islets: in vivo and in vitro studies.
The aim of this work was to study in vivo and in vitro the involvement of macrophages and interleukin-1beta (IL-1beta) in the necrosis of encapsulated islets during xenograft and to evaluate the immunoprotective efficiency of the AN69 membrane. In vivo, 6 days after implantation, 65% of the membrane surface of the devices containing the islets was colonized with macrophages compared with only 5% of the surface of the empty control devices. The morphological aspect of implanted islets was altered and their insulin release decreased significantly compared with freshly isolated ones (265 +/- 50 vs. 507 +/- 81 microU/mL). In vitro, the insulin release of encapsulated islets cultured for 2 days decreased to 32 and 28%, respectively, in the presence of IL-1beta and macrophages. The addition of anti-IL-1beta antibody to the co-culture of macrophages and islets did not modify this loss of functional activity. Furthermore, IL-1beta passed through the AN69 membrane. In conclusion, macrophages are involved in damaging encapsulated pancreatic islets and are probably partly responsible for islet transplantation failure.
Kessler
L
L
Jeune Equipe Médicale Universitaire, Strasbourg, France.
Jesser
C
C
Lombard
Y
Y
Karsten
V
V
Belcourt
A
A
Pinget
M
M
Poindron
P
P
D000818:Animals; D002478:Cells, Cultured; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000379:methods*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D008567:Membranes, Artificial; D051379:Mice; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017208:Rats, Wistar; D014181:Transplantation Immunology; D014183:Transplantation, Heterologous
D007328:Insulin; D007375:Interleukin-1; D008567:Membranes, Artificial