Khalil R M, Luz A, Mailhammer R, Moeller J, Mohamed A A, Omran S, Dörmer P, Hültner L
GSF-Institut für Experimentelle Hämatologie, Munich, Germany.
Infect Immun. 1996 Dec;64(12):4960-6. doi: 10.1128/iai.64.12.4960-4966.1996.
Mast cells and granulocytes-macrophages (GM) are components of the host defense system against worm infections, including schistosomiasis. Here we report the kinetics of changes in the number of colony-forming cells (CFC) for mast cells and GM during the course of a primary experimental infection of mice with Schistosoma mansoni cercariae over a period of 24 weeks postinfection (p.i.). Concurrently, we measured known myelopoietic and/or mast cell-stimulating cytokines (i.e., interleukin 3 [IL-3] and IL-9) in pokeweed mitogen-activated spleen cell-conditioned medium. Our results show that during the acute phase of the hepatic granulomatous reaction, the numbers of both mast-CFC and GM-CFC were significantly elevated in bone marrow. However, while femoral GM-CFC numbers had returned to normal control values at week 16 p.i., femoral and splenic mast-CFC numbers remained significantly elevated until week 20 p.i., which corresponds to the chronic fibrotic phase of hepatic granulomatous inflammation. Increased GM-CFC numbers correlated with elevated IL-3 levels, while increased mast-CFC numbers paralleled the increased IL-9 concentrations in spleen cell-conditioned medium. By the reverse transcription-PCR method, enhanced expression of IL-3 and IL-9 transcripts was found in RNA samples obtained from livers and spleens of infected mice. Our data demonstrate that during the course of infection of mice with S. mansoni, the coordinate need for mast cells and GM is at least partly regulated at the stage of progenitor cell commitment in the bone marrow and spleen. It appears that IL-3 and IL-9 help to promote at this stage the ultimate generation of mature effector cells.
肥大细胞和粒细胞-巨噬细胞(GM)是宿主抵御包括血吸虫病在内的蠕虫感染的防御系统的组成部分。在此,我们报告了在小鼠经曼氏血吸虫尾蚴初次实验感染后的24周内,肥大细胞和GM的集落形成细胞(CFC)数量变化的动力学情况。同时,我们检测了商陆有丝分裂原激活的脾细胞条件培养基中已知的骨髓生成和/或肥大细胞刺激细胞因子(即白细胞介素3 [IL-3]和IL-9)。我们的结果表明,在肝脏肉芽肿反应的急性期,骨髓中肥大细胞CFC和GM-CFC的数量均显著升高。然而,虽然股部GM-CFC数量在感染后第16周已恢复至正常对照值,但股部和脾脏肥大细胞CFC数量在感染后第20周之前仍显著升高,这与肝脏肉芽肿炎症的慢性纤维化阶段相对应。GM-CFC数量的增加与IL-3水平的升高相关,而肥大细胞CFC数量的增加与脾细胞条件培养基中IL-9浓度的增加平行。通过逆转录-PCR方法,在从感染小鼠的肝脏和脾脏获得的RNA样本中发现了IL-3和IL-9转录本的表达增强。我们的数据表明,在小鼠感染曼氏血吸虫的过程中,对肥大细胞和GM的协同需求至少部分在骨髓和脾脏中祖细胞定向分化阶段受到调节。似乎IL-3和IL-9在此阶段有助于促进成熟效应细胞的最终生成。