Department of Pediatric Rheumatology and Immunology, University Children's Hospital Münster, Münster, NRW, Germany.
PLoS One. 2013 Apr 26;8(4):e62761. doi: 10.1371/journal.pone.0062761. Print 2013.
Recent developments suggest a causal link between inflammation and impaired bacterial clearance in Crohn's disease (CD) due to alterations of intestinal macrophages. Studies suggest that excessive inflammation is the consequence of an underlying immunodeficiency rather than the primary cause of CD pathogenesis. We characterized phenotypic and functional features of peripheral blood monocytes of patients with quiescent CD (n = 18) and healthy controls (n = 19) by analyses of cell surface molecule expression, cell adherence, migration, chemotaxis, phagocytosis, oxidative burst, and cytokine expression and secretion with or without lipopolysaccharide (LPS) priming. Peripheral blood monocytes of patients with inactive CD showed normal expression of cell surface molecules (CD14, CD16, CD116), adherence to plastic surfaces, spontaneous migration, chemotaxis towards LTB4, phagocytosis of E. coli, and production of reactive oxygen species. Interestingly, peripheral blood monocytes of CD patients secreted higher levels of IL1β (p<.05). Upon LPS priming we found a decreased release of IL10 (p<.05) and higher levels of CCL2 (p<.001) and CCL5 (p<.05). The expression and release of TNFα, IFNγ, IL4, IL6, IL8, IL13, IL17, CXCL9, and CXCL10 were not altered compared to healthy controls. Based on our phenotypic and functional studies, peripheral blood monocytes from CD patients in clinical remission were not impaired compared to healthy controls. Our results highlight that defective innate immune mechanisms in CD seems to play a role in the (inflamed) intestinal mucosa rather than in peripheral blood.
最近的研究表明，由于肠道巨噬细胞的改变，炎症与克罗恩病（CD）中细菌清除受损之间存在因果关系。研究表明，过度炎症是潜在免疫缺陷的结果，而不是 CD 发病机制的主要原因。我们通过分析细胞表面分子表达、细胞黏附、迁移、趋化性、吞噬作用、氧化爆发以及有无脂多糖（LPS）引发时细胞因子的表达和分泌，来描述处于缓解期的 CD 患者（n=18）和健康对照者（n=19）外周血单核细胞的表型和功能特征。处于不活动期的 CD 患者的外周血单核细胞表现出正常的细胞表面分子（CD14、CD16、CD116）表达、对塑料表面的黏附、自发迁移、对 LTB4 的趋化性、对大肠杆菌的吞噬作用以及活性氧的产生。有趣的是，CD 患者的外周血单核细胞分泌更高水平的 IL1β（p<.05）。在 LPS 引发后，我们发现 IL10 的释放减少（p<.05），CCL2（p<.001）和 CCL5（p<.05）水平升高。与健康对照者相比，TNFα、IFNγ、IL4、IL6、IL8、IL13、IL17、CXCL9 和 CXCL10 的表达和释放没有改变。基于我们的表型和功能研究，处于临床缓解期的 CD 患者的外周血单核细胞与健康对照者相比没有受损。我们的结果强调，CD 中先天免疫机制的缺陷似乎在（发炎的）肠黏膜中起作用，而不是在外周血中。
