MACROPHAGE CYTOTOXICITY TOWARDS ISOLATED RAT ISLET CELLS - NEITHER LYSIS NOR ITS PROTECTION BY NICOTINAMIDE ARE BETA-CELL SPECIFIC

In animal models of Type 1 (insulin-dependent) diabetes mellitus macrophages were shown to be the first immunocytes that infiltrate the pancreatic Langerhans islets in the autoimmune process. We now show direct macrophage cytotoxicity against isolated rat islet cells in an electron microscopical study, which permits investigation of the specificity of this process. Freshly isolated islet cells were co-incubated with syngeneic peritoneal macrophages at a target: effector-cell ratio of 1:2. After various time periods, the cells were directly fixed and embedded; the ratio of live and dead cells was evaluated by electron microscopy. Our results demonstrate that activated but not resident macrophages lyse islet cells in a time-dependent manner. After 15 h of co-incubation lysis of islet cells is complete. No islet cell-macrophage contacts and no differences between the lysis of Beta cells or non-Beta cells were observed during the observation period. Islet cells encapsulated in alginate were also lysed by macrophages as a direct proof for soluble mediator(s) of cytotoxicity. Nicotinamide protected islet cells from lysis in a dose-dependent manner. As a result of this electron microscopic study we conclude that even at very low target: effector ratios, activated macrophages lyse syngeneic islet cells regardless of islet cell type via secretion of humoral mediator(s).