We have investigated the mechanisms whereby Escherichia coli endotoxin exerts its exudative effects, by using an isolated rat mesentery placed as a separation membrane between the two compartments of a diffusion cell. The permeability coefficient of albumin (PA) can be easily computed from the equilibration rate of 125I-labeled albumin added to one compartment. E. coli endotoxin increased PA in a concentration-related manner. Direct measurements revealed an early and transient increase in cyclic AMP and prostaglandin E-immunoreactive material. These effects of endotoxin could be inhibited by indomethacin. Calcium-depleted tissues have a low PA, even though cyclic AMP levels could still be increased by endotoxin. It incubations were prolonged beyond 90 min, PA remained elevated, but prostaglandin E and cyclic AMP levels fell to control values. Similar results were observed with trypsin-treated tissues. These results suggest that transmesenteric passage of albumin is increased in the presence of endotoxin. During the earlier part of the incubation (up to 90 min), the effects could be related to a local synthesis of prostaglandin E, and are controlled by cyclic AMP and intracellular calcium levels. During longer incubations (90-280 min) mesothelial exfoliation could occur, allowing free diffusion of albumin through the remaining interstitial tissue.
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