Colonic mucosa barrier defects in collagenous and ischemic colitis.

Abstract

The subepithelial myofibroblasts (SEMFs) and the subepithelial band of macrophages (SEBM) are major components of the colonic mucosa barrier. Although their role in homeostasis is widely recognized, their contribution to disease states is largely unknown. Our aim was to explore histological characteristics of SEMFs and SEBM in collagenous and ischemic colitis in order to identify specific changes in distinct mucosa backgrounds lacking significant inflammation. SEMFs, SEBM and lamina propria (LP) macrophages were identified immunohistochemically by alpha smooth muscle Actin and Cluster of Differentiation 68 respectively in 38 colonic biopsies [14 collagenous colitis (CC), 14 ischemic colitis (IC), 10 normal mucosa]. In CC, SEMFs were rarely detectable in the collagenous band while aSMA-negative pericryptal fibroblast-like cells appeared. In lower LP interconnecting SEMFs processes were formed. SEBM was preserved in areas with a collagenous layer up to 20 μm. In thicker layers, it was fragmented and gradually disappeared in parallel with engulfment of enlarged macrophages. LP macrophages were usually increased. In IC, slight SEMFs changes preceded discernible epithelial alterations. Rounding, disintegration and extinction of SEMFs constituted successive alterations coinciding with crypt shrinkage and denudation. SEBM displayed total or almost total abolishment in areas with crypt damage but also in sites with minimal changes and in adjacent normal mucosa. Our findings provide evidence of impairment of both mucosa barrier constituents in CC and IC. In CC, histological alterations are closely related to the collagenous layer which seems to affect SEMFs differentiation and migration as well as SEBM integrity. The early extinction of SEBM in IC is indicative of its high sensitivity to hypoxia and hypoperfusion.