Essential contribution of macrophages to islet cell destruction in vivo and in vitro.

A number of observations indicate an essential role of macrophage activity in the development of hyperglycemia in animal models of Type I diabetes. Administration of macrophage-toxic silica particles prevents spontaneous diabetes development in BB rats or NOD mice. The same result was noted in the low-dose streptozotocin-induced diabetes model in mice. Macrophages appear to be the first immune cells infiltrating islets during early insulitis. Macrophages in inflamed islets of BB rats bear the ED1 marker, whereas resident islet macrophages are ED2-positive. In vitro, ED1-positive macrophages were found to lyse pancreatic islet cells to a similar degree to various tumor cells but not normal thyrocytes. Macrophage-mediated lysis of islet cells was inhibited in the presence of 10-100 mM nicotinamide.