M2 macrophages and phenotypic modulation of intestinal smooth muscle cells characterize Inflammatory stricture formation in the rat.

M2 macrophages and phenotypic modulation of intestinal smooth muscle cells characterize Inflammatory stricture formation in the rat. Am J Pathol. 2020 May 29;: Authors: Lourenssen SR, Blennerhassett MG Abstract The progression of Crohn's disease to intestinal stricture formation is poorly controlled and the pathogenesis is unclear, although increased smooth muscle mass is present. Earlier, stricture formation was described in in the rat model of TNBS-induced colitis, now re-examined for early cellular features of stricture development. While inflammation of the mid-descending colon typically resolved, a subset showed characteristic stricturing by Day 16, with an inflammatory infiltrate in the neuromuscular layers that included eosinophils, CD3-positive T cells and CD68-positive macrophages. Closer study identified CD163-positive, CD206-positive and arginase-positive cells indicative of a M2 macrophage phenotype. Stricturing involved ongoing proliferation of intestinal smooth muscle cells (ISMC) with expression of PDGF-Rβ and progressive loss of phenotypic markers, and stable expression of HIF-1α. In parallel, collagen I and III showed a selective and progressive increase over time. A culture model of the stricture phenotype of ISMC showed stable HIF-1α expression that promoted growth and improved both survival and growth in models of experimental ischemia. This phenotype was hyperproliferative to serum and PDGF-BB and unresponsive...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research