结肠炎
炎症性肠病
过继性细胞移植
微小膜壳绦虫
脾脏
免疫学
炎症
巨噬细胞
川地68
化学
体外
药理学
病理
生物
医学
免疫系统
T细胞
生物化学
免疫组织化学
疾病
绦虫
蠕虫
作者
M Hunter,Arthur Wang,Kuljit Parhar,Michael Johnston,Nico van Rooijen,Paul L. Beck,Derek M. McKay
标识
DOI:10.1053/j.gastro.2009.12.041
摘要
Infection with the rat tapeworm Hymenolepis diminuta reduces the severity of dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice. Infection with H. diminuta increases colonic expression of arginase-1 and found in inflammatory zone 1 (FIZZ1), markers of alternatively activated macrophages (AAMs). We investigated whether AAMs have anticolitic effects.Normal or macrophage-depleted Balb/c mice were infected with H. diminuta; some mice were given DNBS, and the severity of colitis was assessed by disease activity scores, myeloperoxidase activity, and histologic examination. AAMs were also differentiated in vitro, given to mice by intraperitoneal or intravenous injection, and the effects on DNBS-induced colitis were determined. Numbers of AAMs were assessed in biopsy specimens from patients with Crohn's disease.Depletion of intestinal macrophages using clodronate-liposomes prevented the anticolitic effect of infection with H. diminuta. Injection of AAMs, but not classically activated macrophages, significantly reduced the severity of DNBS-induced colitis. The AAM-induced, anticolitic effect was accompanied by increased interleukin (IL)-10 production from mitogen-stimulated spleen cells; in vivo neutralization of IL-10 partially reduced the effects of AAM transfer. Patients with active CD had reduced numbers of CD68(+)CD206(+) macrophages (which indicate AAM), whereas biopsy specimens from patients with inactive CD had increased numbers of these cells.Analysis of the H. diminuta-murine DNBS system identified the AAM, which, when administered to mice, significantly reduced DNBS-induced colitis. The ability to derive AAMs from patients' blood suggests that adoptive transfer of these cells could be a novel approach to inflammatory bowel disease.
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