THE ROLE OF INFILTRATING MACROPHAGES IN ISLET DESTRUCTION AND REGROWTH IN A TRANSGENIC MODEL

The expression of interferon-gamma (IFN-gamma) in pancreatic beta cell s leads to a complex pathology that represents the processes of both i slet destruction and islet regeneration. Inflammatory cells and the fa ctors elicited from them participate in the development of pathology i n this transgenic model. To dissect the role of infiltrating macrophag es in these events, the monoclonal directed against the type 3 complem ent receptor (5C6) was utilized to inhibit the extravasation of macrop hages. This was approached by treating transgenic mice with 5C6 for 3 or 4 months, starting from 5-7 days of age. The data presented in this report demonstrate that infiltrating macrophages are important in the observed induction of diabetes in our transgenic model. We also found that infiltrating macrophages did not play a major role in the observ ed proliferation and islet regeneration, but some interesting subtleti es regarding the regulation of this proliferative process emerged. (C) 1995 Academic Press Limited