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 calciumbinding 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 þ cells, which were only present in HUC patients, were characterised by increased expression of lysozyme, inducible nitric oxide synthase and CD204. This indicates PAS þ 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.

Changes in duodenal CD163-positive cells in dogs with chronic enteropathy after successful treatment

“…We found that healthy dogs had a higher number of CD163 + than CAL + cells both in villi and crypts, which is consistent with previous observations in dogs with histiocytic ulcerative colitis and CE. 21,32 Furthermore, CD163 + was decreased in dogs with IRE prior to treatment compared with CTRL dogs as reported recently in dogs with CE where information about treatment response is unknown. 21 Response to treatment in both FRE and IRE dogs was characterized by an increase in CD163 + (significant in IRE dogs).…”

“…Most studies in dogs to date have assessed intestinal Mϕ using CAL expression only, except for two recent studies assessing CAL with other putative Mϕ markers in dogs with histiocytic ulcerative colitis or chronic enteropathy. 11,12,14,21,32…”

“…33 There is some evidence that CAL expression is lost during maturation of canine Mϕ; for example, in dogs with leishmaniasis, Mϕ with amastigotes are CAL negative and in granulomatous colitis, PAS positive Mϕ are also CAL negative. 16,32 This suggests that CAL expression might be more suited to assess migrating monocytes and early stages of Mϕ maturation, rather than resident Mϕ -population.…”

Escherichia coli-induced granulomatous colitis in a cat

“…2,3,5 In canine cases, macrophage heterogeneity suggests a difference in function compared with healthy individuals. 6…”

Metastatic immune infiltrates correlate with those of the primary tumour in canine osteosarcoma

“…T‐cells, FOXP3+ cells, B‐cells and macrophages, were detected using anti‐CD3 (1:50; rat anti‐human, CD3‐12; Moore Lab; Davis, California), anti‐FOXP3 (1:25; rat anti‐mouse/rat, FJK‐16S; Thermo Fisher Scientific; San Diego, California), anti‐Pax‐5 (1:50; 24/Pax‐5; BD Biosciences; San Jose, California), and anti‐CD204 (1:400; mouse anti‐human, SRA‐E5; Cosmo Bio; Carlsbad, California), respectively. The anti‐CD3 and ‐FOXP3 clones are stated as canine cross‐reactive by their manufacturers, while the anti‐Pax‐5 and ‐CD204 have shown canine cross‐reactivity in several previous studies . The ImmPRESS horseradish peroxidase (HRP) polymer detection kit was used for primary antibody detection (anti‐mouse IgG, MP‐7452; anti‐rat IgG, MP‐7444; Vector; Burlingame, CA), and Vector NovaRed HRP substrate kit (Vector; Burlingame, California) was used for chromogen development.…”