Primary nonfunction of islet xenografts: the role of macrophages.
Primary nonfunction (PNF) of hamster islets occurs when they are transplanted under the kidney capsule of diabetic Lewis rat recipients. PNF is absent if the islets are grafted into the liver. Previous results have indicated that macrophages might be involved in the phenomenon of PNF. To test this hypothesis, two procedures affecting macrophages were employed. First, recipients were pretreated with liposomes containing dichloromethylene disphosphonate (L-MDP), killing macrophages upon phagocytosis. Second, recipients were pretreated with the arginine analogue, L-NA, in order to inhibit the synthesis of nitric oxide (NO), a molecule believed to mediate beta cell dysfunction. Injection of L-MDP into the peritoneal cavity had no effect on PNF. However, co-transplantation of L-MDP with hamster islets under the kidney capsule reduced PNF significantly. Eradication of Kupffer cells with L-MDP did not prolong the survival of islets transplanted into the liver, indicating that acute xenogeneic rejection in this model is not mediated by macrophages. A single injection of L-NA, 3 h before transplantation resulted in complete annihilation of PNF, all recipients became normoglycemic within 1 day and remained so for 1.4+/-0.5 days. These results confirmed the finding that macrophages and NO play a crucial role in PNF of islet grafts.
Laboratory for Experimental Surgery, Erasmus University, Rotterdam, The Netherlands.
R L
RL
Marquet
F
F
Bonthuis
M
M
van IJken
E
E
Bouwman
M C
MC
Wolvekamp
N
N
van Rooijen
M
M
Scheringa
J N
JN
IJzermans
D000818:Animals; D004002:Clodronic Acid / Q000494:pharmacology; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D005260:Female; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000502:physiology*; D007668:Kidney; D008081:Liposomes; D008099:Liver; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008647:Mesocricetus; D019335:Nitroarginine / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D014183:Transplantation, Heterologous / Q000276:immunology / Q000502:physiology*; D016042:Transplantation, Heterotopic
D008081:Liposomes; D004002:Clodronic Acid; D019335:Nitroarginine