Ghanem Lobna Y, Dahmen Uta, Dirsch Olaf, Nosseir Mona Mf, Mahmoud Soheir S, Mansour Wafaa Af
Lobna Y Ghanem, Department of Electron Microscope, Theodor Bilharz Research Institute, PO Box 30 Imbaba, Giza 12411, Egypt.
World J Hepatol. 2010 Dec 27;2(12):434-41. doi: 10.4254/wjh.v2.i12.434.
To introduce Granulocyte-colony stimulating factor (G-CSF) as a new therapeutic modality for schistosomiasis through stem cell mobilization, immunomodulation or fibrosis remodeling.
In this study, a 5 d course of human recombinant G-CSF (100 μg/kg sc) was applied to Schistosoma mansoni-infected mice at different stages of disease (5 d before infection as well as 3, 5 and 7 wk post-infection). The animals were sacrificed at 10 d as well as 4, 6 and 8 wk post infection. Mice were examined for: (1) Total leukocyte count which is an accepted surrogate marker for the stem cell mobilization into the circulation; (2) Egg count in intestine and liver tissue to assess the parasitic load; and (3) Histopathological changes in Hx/E and Masson trichrome stained sections as well as collagen content in Sirius red-stained liver sections to determine the severity of liver fibrosis.
Mice developed leukocytosis. The egg load and the number of granulomas were not affected by the G-CSF treatment but there was an obvious change in the composition of granulomas towards an increased cellularity. Moreover, fibrosis was significantly decreased in treated groups compared to untreated animals (collagen content either preinfection or at 3 and 5 wk post infection: 5.8 ± 0.5, 4.7 ± 0.5, 4.0 ± 0.7 vs 8.2 ± 0.9; P ≤ 0.01).
Although G-CSF did not cause direct elimination of the parasite, it enhanced granulomatous reaction and reduced the fibrosis. Further investigation of the underlying mechanisms of these two actions is warranted.
介绍粒细胞集落刺激因子(G-CSF)作为一种通过干细胞动员、免疫调节或纤维化重塑治疗血吸虫病的新方法。
在本研究中,将5天疗程的重组人G-CSF(100μg/kg皮下注射)应用于曼氏血吸虫感染小鼠,给药时间为疾病的不同阶段(感染前5天以及感染后3、5和7周)。在感染后10天以及4、6和8周处死动物。检测小鼠:(1)白细胞总数,这是干细胞动员入循环的公认替代标志物;(2)肠道和肝脏组织中的虫卵计数,以评估寄生虫负荷;(3)苏木精/伊红(Hx/E)和Masson三色染色切片的组织病理学变化以及天狼星红染色肝脏切片中的胶原含量,以确定肝纤维化的严重程度。
小鼠出现白细胞增多。G-CSF治疗未影响虫卵负荷和肉芽肿数量,但肉芽肿的组成有明显变化,细胞增多。此外,与未治疗动物相比,治疗组的纤维化明显减轻(感染前或感染后3周和5周的胶原含量:5.8±0.5、4.7±0.5、4.0±0.7 vs 8.2±0.9;P≤0.01)。
虽然G-CSF未直接清除寄生虫,但它增强了肉芽肿反应并减轻了纤维化。有必要进一步研究这两种作用的潜在机制。