In vitro studies of intestinal endotoxin absorption. I. Kinetics of absorption in the isolated everted gut sac.

Previous studies have shown in a qualitative manner that endotoxin can cross gut epithelium, but precise quantitation has not been possible. The present studies were undertaken to measure quantitatively the mucosal to serosal unidirectional flux of endotoxin with the use of an in vitro rat gut sac preparation. 51Cr-Labeled endotoxin was placed in the mucosal bath in concentrations ranging from 0.05 to 2.0 mg per ml. Over a 2-hr period of time, a small amount of endotoxin was transported transmurally, which was shown chromatographically to be similar to the starting material and which retained its toxic and immunogenic properties. It was first shown that the presence of 2.0 mg per ml of endotoxin in the mucosal bath did not significantly alter the tissue's histology or permeability to 3-O-methyl-D-glucose. When unidirectional fluxes were measured, it was found that the flux was not proportional to the endotoxin concentration as would be expected with a passively permeable solute, but rather its transport system became "saturated," displaying a maximum transport rate of 4.72 (mug per cm) per 2 hr and a Km of 0.425 mg per ml. The isolated gut sac provides an excellent model for the precise study of factors involved in endotoxin absorption.