Aref Salah, El Refaei M F, Sakrana M, El-Nemre H
Hematology Department, Mansoura Faculty of Medicine, Mansoura University, Egypt.
Hematology. 2004 Feb;9(1):71-8. doi: 10.1080/10245330310001652482.
Enhanced neutrophil apoptosis has been reported in neutropenic hepatosplenic schistosomiasis. The shortening of neutrophil survival via apoptosis may explain the neutropenia that occur in these patients. However, the regulation of neutrophil apoptosis in hepatosplenic schistosomiasis has not been clearly defined. Neutrophils harvested from neutropenic patients with hepatosplenic (HS) schistosomiasis, (n=25), non-neutropenic patients with hepatointestinal (HI) schistosomiasis (n=10), and age-/gender-matched healthy control subjects (n=10) were incubated with autologous serum. Neutrophils apoptosis was quantified by flow cytometry through determination of propidium iodide nuclear staining and confirmed by DNA gel electrophoresis at 0 (i.e. fresh neutrophils), 4 and 24 h culture. Neutrophils from healthy subjects were also incubated with either 10% heterologous normal or neutropenic serum, with and without anti-Fas ligand antibody. Fas expression was assessed in fresh neutrophils using flow cytometry. Compared with normal healthy neutrophils, and HI neutrophils, neutropenic neutrophils demonstrated greater apoptosis in the presence of autologous serum (P<0.01, 0.05, respectively). Furthermore, compared with normal neutrophils exposed to heterologous normal serum, those exposed to heterologous neutropenic serum exhibited higher apoptosis rates ( P<0.01). Moreover, anti-Fas L antibody attenuated the neutropenic serum-induced neutrophil apoptosis in normal neutrophils. Fas expression was significantly higher in the neutropenic group when compared to both HI and normal healthy controls (P<0.05). In addition, Fas expression by neutrophils was paralleled by high neutrophil apoptosis. On the other hand, neutrophil apoptosis was not correlated to the size of spleen in neutropenic group. In conclusion, the rate of neutrophil apoptosis is accelerated in patients with neutropenic hepatosplenic schistosomiasisis. These findings suggest that the enhanced neutrophil apoptosis that occurs in neutropenic HS patients is triggered by a serum factor, which is mostly a Fas ligand.
据报道，在中性粒细胞减少的肝脾型血吸虫病中，中性粒细胞凋亡增强。通过凋亡导致中性粒细胞存活时间缩短，可能解释了这些患者出现的中性粒细胞减少。然而，肝脾型血吸虫病中中性粒细胞凋亡的调控机制尚未明确。从25例中性粒细胞减少的肝脾型（HS）血吸虫病患者、10例非中性粒细胞减少的肝肠型（HI）血吸虫病患者以及年龄和性别匹配的10例健康对照者中采集中性粒细胞，与自体血清一起孵育。通过流式细胞术检测碘化丙啶核染色来定量中性粒细胞凋亡，并在培养0小时（即新鲜中性粒细胞）、4小时和24小时时通过DNA凝胶电泳进行确认。健康受试者的中性粒细胞也与10%的异源正常血清或中性粒细胞减少血清一起孵育，同时加入或不加入抗Fas配体抗体。使用流式细胞术评估新鲜中性粒细胞中的Fas表达。与正常健康中性粒细胞和HI中性粒细胞相比，中性粒细胞减少的中性粒细胞在自体血清存在的情况下表现出更大程度的凋亡（分别为P<0.01和P<0.05）。此外，与暴露于异源正常血清的正常中性粒细胞相比，暴露于异源中性粒细胞减少血清的中性粒细胞凋亡率更高（P<0.01）。而且，抗Fas L抗体减弱了中性粒细胞减少血清诱导的正常中性粒细胞凋亡。与HI和正常健康对照组相比，中性粒细胞减少组中的Fas表达显著更高（P<0.05）。此外，中性粒细胞的Fas表达与高中性粒细胞凋亡平行。另一方面，中性粒细胞减少组中中性粒细胞凋亡与脾脏大小无关。总之，中性粒细胞减少的肝脾型血吸虫病患者中性粒细胞凋亡速率加快。这些发现表明，中性粒细胞减少的HS患者中增强的中性粒细胞凋亡是由一种血清因子触发的，该血清因子主要是Fas配体。
