Heterogeneity of macrophages in canine histiocytic ulcerative colitis

Abstract

Histiocytic ulcerative colitis (HUC) is a chronic enteropathy which most notably occurs in Boxer dogs and French bulldogs. The inflamed mucosa is hallmarked by large, foamy, periodic acid-Schiff (PAS)-positive macrophages infiltrating the colonic mucosa. As little is known about their origin and phenotype, an immunohistochemical study was performed using different macrophage markers. Generally, canine colonic macrophages showed high expression of ionised calcium-binding adaptor molecule 1 and MHC class II. In canine HUC, macrophages revealed up-regulation of lysozyme and L1 Ag but decreased CD163 expression compared with controls, suggesting them to be pro-inflammatory cells, whereas the healthy colonic mucosa was characterised by an anti-inflammatory macrophage phenotype. In addition, PAS reaction was used to discriminate macrophage subpopulations. PAS- macrophages displayed higher expression of L1 Ag and CD64, whereas PAS+ cells, which were only present in HUC patients, were characterised by increased expression of lysozyme, inducible nitric oxide synthase and CD204. This indicates PAS+ cells to be mature macrophages contributing to the inflammatory process, which are most likely maintained by differentiation of immature PAS- macrophages continuously recruited from blood monocytes. In summary, macrophage heterogeneity in canine HUC probably illustrates their different maturation states and functions compared with the healthy animals.