Lim Daejin, Kim Hee Kyung, Jeong Jae-Ho, Jung Yoon Seok, Lee Shee Eun, Jang Hee-Chang, Jung Sook-In, Choi Hueng-Sik, Rhee Joon Haeng, Lee Sung-Gwon, Park Chungoo, Song Miryoung, Choy Hyon E
Department of Microbiology, Chonnam National University Medical School, Gwangju 61468, Korea.
Department of Molecular Medicine (BK21plus), Chonnam National University Graduate School, Gwangju 61468, Korea.
Microorganisms. 2020 Apr 29;8(5):646. doi: 10.3390/microorganisms8050646.
Neutropenic sepsis is a fatal consequence of chemotherapy, and septic complications are the principal cause of mortality. Chemotherapy-induced neutropenia leads to the formation of microscopic ulcers in the gastrointestinal epithelium that function as a portal of entry for intraluminal bacteria, which translocate across the intestinal mucosal barrier and gain access to systemic sites, causing septicemia. A cyclophosphamide-induced mouse model was developed to mimic the pathophysiologic sequence of events that occurs in patients with neutropenic sepsis. The TLR5 agonist bacterial flagellin derived from extended the survival of cyclophosphamide-treated mice by reducing the bacterial load in internal organs. The protective effect of flagellin was mediated by the antimicrobial protein lipocalin 2 (Lcn2), which is induced by TLR5-NF-κB activation in hepatocytes. Lcn2 sequestered iron from infecting bacteria, particularly siderophore enterobactin-dependent members of the family, thereby limiting their proliferation. Lcn2 should be considered for the treatment of neutropenic sepsis and gastrointestinal damage during chemotherapy to prevent or minimize the adverse effects of cancer chemotherapy.
中性粒细胞减少性败血症是化疗的致命后果，败血症并发症是主要死因。化疗引起的中性粒细胞减少会导致胃肠道上皮形成微小溃疡，这些溃疡成为腔内细菌的入口，细菌穿过肠道黏膜屏障进入全身部位，引发败血症。构建了环磷酰胺诱导的小鼠模型，以模拟中性粒细胞减少性败血症患者发生的病理生理事件序列。源自 的Toll样受体5（TLR5）激动剂细菌鞭毛蛋白通过减少内脏器官中的细菌载量，延长了环磷酰胺处理小鼠的存活时间。鞭毛蛋白的保护作用由抗菌蛋白脂质运载蛋白2（Lcn2）介导，Lcn2由肝细胞中TLR5-核因子κB（NF-κB）激活诱导产生。Lcn2从感染细菌中螯合铁，特别是 家族中依赖铁载体肠杆菌素的成员，从而限制它们的增殖。在化疗期间治疗中性粒细胞减少性败血症和胃肠道损伤时，应考虑使用Lcn2，以预防或尽量减少癌症化疗的不良反应。
