Figure 3. Computational modeling of colonic NO concentration.

A. Schematic representation of colonic crypt anatomy. The inner lining of the colonic mucosa consists of three distinct layers: the muscularis mucosa, the lamina propria, and the epithelium. B. NO concentration as a function of height above crypt base taking into account NO synthesis by macrophages and epithelial cells. The NO synthesis rate per unit volume in epithelial cells was assumed here to be 5.6 µM/s, the same as the baseline rate for macrophages. This is a conservative value; it is conceivable that rates in vivo are much higher. Axial concentration variations are shown for radial positions r = 0, 18, 32 µm, which corresponds to the center of the luminal fluid, middle of the epithelium, and middle of the lamina propria region, respectively. C. Time-dependent NO concentration and cumulative NO dose experienced by an epithelial cell as it migrates from the crypt base to the mucosal surface. The total time for migration was assumed to be 96 h. The ‘monolayer model’ assumes that the main source of NO is a confluent monolayer of macrophages localized in the region below the crypt base (see A.), whereas the ‘monolayer + distributed model’ assumes that macrophages are also distributed throughout the lamina propria. Reprinted from [72] (with permission of Elsevier).