Macromolecular absorption by histologically normal and abnormal small intestinal mucosa in childhood: an in vitro study using organ culture.

Knowledge of the mechanism of macromolecular absorption in the small intestine is based largely on animal studies. We have attempted to assess qualitatively and quantitatively the amount and the mechanism of uptake of horseradish peroxidase (HRP), a model macromolecule, in human small intestine, employing biopsy material from children undergoing gastrointestinal investigations. The biopsy material was incubated in culture medium containing HRP, and a comparison was made between histologically normal and histologically abnormal biopsies. In the normal specimens HRP was detected in pinocytotic vesicles along the villous epithelium. It was also seen in multivesicular bodies and in the interepithelial cell spaces at the base and tip of the villus. These latter areas corresponded to regions where damaged and extruding enterocytes, diffusely penetrated by HRP, were seen. This demonstrates that intact macromolecules can be taken up by normal small intestine in vitro in childhood and indicates two possible routes of antigen entry: (a) by active absorption through intact enterocytes and (b) through damaged or extruding cells. In the abnormal specimens the distribution of HRP was more varied. Most specimens showed an increased presence of HRP in the interepithelial cell spaces and an increased number of enterocytes diffusely penetrated by HRP, but a decrease in pinocytosis in the most severely abnormal enterocytes. An increase in HRP was also observed in the basement membrane and, in one instance, within capillaries of the lamina propria. It was concluded that when an enteropathy is present, an increase in mucosal permeability to macromolecules may result. This is most likely due to an increase in the passive diffusion of macromolecules into the mucosa.