Differential Effects of Mucosal pH on Human (Caco-2) Intestinal Epithelial Cell Motility, Proliferation, and Differentiation

Mucosal pH abnormalities are associated withanastomotic dehiscence, ischemia, and malignancy. Wepostulated that intraluminal pH influences intestinalepithelial motility, proliferation, and differentiation and studied extracellular pHo(7.0-8.5) effects on human (Caco-2) intestinalepithelial motility, proliferation, and differentiation.Mucosal healing was modeled by sheet migration anddifferentiation by alkaline phosphatase and dipeptidyl dipeptidasespecific activity. In parallel differentiation andmotility studies, we inhibited proliferation withmitomycin to dissociate indirect mitogenic effects.Intracellular pHi was quantitated using BCECF/AMat varying extracellular pHo and in migratingcells. Motility was maximal at pHo 7.6 andproliferation at 7.2. Each decreased with acidity andalkalinity. By contrast, brush border enzyme activity was lowest atpHo 7.0 and highest at pHo 8.5.pHi was highest at pHo 8.5.Migrating cell pH was higher than static cellpHi. Thus, extracellular pHodeviations perturb Caco-2 pH homeostasis and motility. Alkalinitypromotes differentiation while acidity inducesproliferation and limits differentiation.