PANCREAS-SPECIFIC VENULAR LABELING BY MONASTRAL BLUE-B IN THE BB RAT - MODULATION BY PROSTAGLANDINS AND THEIR INHIBITORS

Leaky blood vessels in the microcirculation can be detected in vivo by injecting an animal with colloidal pigments like Monastral blue B (Mb B). We have previously used this labeling method in the BB rat, an ani mal model of spontaneous autoimmune diabetes, and detected increased v ascular permeability restricted to the venules of the pancreas. The ea rlier data suggested that pancreata of animals susceptible to labeling contain trapped intravascular monocytes that are activated to release vasoactive mediators after phagocytosis of MbB. To explore these obse rvations further, we investigated the effects of prostaglandins on thi s system. Prostaglandins are known to be important mediators of inflam matory responses and to modulate the expression of disease in other an imal models of autoimmunity, We now report that MbB-induced pancreatic labeling is modulated by misoprostol (an analogue of prostaglandin E1 ), prostaglandins of the E series, and inhibitors of prostaglandin syn thesis. The nonsteroidal anti-inflammatory drugs ibuprofen and ketorol ac both reduced the intensity of labeling in susceptible BB rats in a dose dependent manner. In contrast, both misoprostol and prostaglandin E2 given at low doses induced pancreatic permeability in the labeling -resistant Wistar Furth rat. To extend this finding, we also tested mu ch higher drug doses, since at high concentrations, E series prostanoi ds exert anti-inflammatory effects. We observed that large doses of pr ostaglandin E1, prostaglandin E2, and misoprostol all suppressed label ing in the BB rat. We conclude that presence of MbB in the pancreatic circulation of the rat induces organ specific venular leakage by an in flammatory process involving prostaglandins.