Khandagale Avinash, Kittner Jens M, Mann Amrit, Ascher Stefanie, Kollar Bettina, Reinhardt Christoph
Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Biol Open. 2018 Jul 25;7(7):bio034140. doi: 10.1242/bio.034140.
Patients with inflammatory bowel disease (IBD) are susceptible to thromboembolism. Interestingly, IBD occurs less frequently in patients with inherited bleeding disorders. Therefore, we analyzed whether -deficiency is protective against the onset of acute colitis in a genetic hemophilia B mouse model. In the 3.5% dextran sulfate sodium (DSS)-induced colitis model, -deficient mice were protected from body-weight loss and had a reduced disease activity score. We detected decreased colonic myeloperoxidase activity and decreased CXCL1 levels in DSS-treated -deficient mice compared with wild-type (WT) littermate controls, indicating decreased neutrophil infiltration. Remarkably, we identified expression of coagulation factor IX (FIX) protein in small intestinal epithelial cells (MODE-K). In epithelial cell cultures, cellular FIX protein expression was increased following stimulation with the bacterial Toll-like receptor agonists lipopolysaccharide, macrophage-activating lipopeptide-2 and Pam3CSK4. Thus, we revealed a protective role of -deficiency in DSS-induced colitis and identified the intestinal epithelium as a site of ectopic FIX.This article has an associated First Person interview with the first author of the paper.
炎症性肠病（IBD）患者易发生血栓栓塞。有趣的是，遗传性出血性疾病患者中IBD的发病率较低。因此，我们在遗传性B型血友病小鼠模型中分析了因子缺乏是否对急性结肠炎的发病具有保护作用。在3.5%葡聚糖硫酸钠（DSS）诱导的结肠炎模型中，因子缺乏的小鼠体重未减轻，疾病活动评分降低。与野生型（WT）同窝对照相比，我们检测到DSS处理的因子缺乏小鼠结肠髓过氧化物酶活性降低，CXCL1水平降低，表明中性粒细胞浸润减少。值得注意的是，我们在小肠上皮细胞（MODE-K）中发现了凝血因子IX（FIX）蛋白的表达。在上皮细胞培养中，用细菌Toll样受体激动剂脂多糖、巨噬细胞激活脂肽-2和Pam3CSK4刺激后，细胞FIX蛋白表达增加。因此，我们揭示了因子缺乏在DSS诱导的结肠炎中的保护作用，并确定肠上皮为异位FIX的位点。本文配有对该论文第一作者的第一人称访谈。
