The effect of ischemic villus cell damage on crypt cell proliferation in the small intestine: evidence for a feedback control mechanism.

In recent years the hypothesis that the number of villus cells regulates crypt cell proliferation in the epithelium of the small intestine has been brought forward by a number of investigators. To test this hypothesis, the villus cell population was reduced by clamping the superior mesenteric artery and vein in rats for 1 hr and the effects on the intestinal epithelium were studied during the first 24 hr. It was shown that temporary interruption of the blood flow to the small intestine led to a marked decrease in the number of functional villus cells within 2 hr; preferentially, cells from the upper part of the villus were lost and the number of crypt cells was not affected. This reduction in the number of villus cells led to an increase in the percentage of labeled crypt cells after pulse labeling with [3H]thymidine, and an expansion of the proliferative cell compartment in the crypt. After a peak of proliferative activity at 16 hr, the investigated crypt cell kinetic parameters approached control values after 24 hr, as did the number of villus cells. The enzyme activities of nonspecific esterase and neutral alpha-glucosidase showed marked decreases in isolated crypt and villus cell compartments as crypt cell proliferation increased. These data support the view that the feedback control of crypt cell proliferation by the functional villus cells, and confirm earlier data on the influence of changing cell kinetics on crypt cell maturation. Additional data which were obtained after creating temporary ischemia in part of the small intestine support the hypothesis of a feedback control of crypt cell proliferation by the functional villus cells, and confirm earlier data on the influence of changing cell kinetics on crypt cell maturation. Additional data which were obtained after creating temporary ischemia in part of the small intestine support the view that the feedback control of proliferation by the villus cells is a local control mechanism.