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

The expression of interferon-gamma (IFN-gamma) in pancreatic beta cells leads to a complex pathology that represents the processes of both islet destruction and islet regeneration. Inflammatory cells and the factors elicited from them participate in the development of pathology in this transgenic model. To dissect the role of infiltrating macrophages in these events, the monoclonal directed against the type 3 complement receptor (5C6) was utilized to inhibit the extravasation of macrophages. 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 observed proliferation and islet regeneration, but some interesting subtleties regarding the regulation of this proliferative process emerged. (C) 1995 Academic Press Limited