DIFFERENTIAL-EFFECTS OF MUCOSAL PH ON HUMAN (CACO-2) INTESTINAL EPITHELIAL-CELL MOTILITY, PROLIFERATION, AND DIFFERENTIATION

Mucosal pH abnormalities are associated with anastomotic dehiscence, i schemia, and malignancy. We postulated that intraluminal pH influences intestinal epithelial motility, proliferation, and differentiation an d studied extracellular pH(o) (7.0-8.5) effects on human (Caco-2) inte stinal epithelial motility, proliferation, and differentiation. Mucosa l healing was modeled by sheet migration and differentiation by alkali ne phosphatase and dipeptidyl dipeptidase specific activity. In parall el differentiation and motility studies, we inhibited proliferation wi th mitomycin to dissociate indirect mitogenic effects. Intracellular p H(i) was quantitated using BCECF/AM at varying extracellular pH(o) and in migrating cells. Motility was maximal at pH(o) 7.6 and proliferati on at 7.2. Each decreased.with acidity and alkalinity. By contrast, br ush border enzyme activity was lowest at pH(o) 7.0 and highest at pH(o ) 8.5. pH(i) was highest at pH(o) 8.5. Migrating cell pH(i) was higher than static cell pH(i). Thus, extracellular pH(o) deviations perturb Caco-2 pH(i) homeostasis and motility. Alkalinity promotes differentia tion while acidity induces proliferation and limits differentiation.