Donaldson L E, Schmitt E, Huntley J F, Newlands G F, Grencis R K
Immunology Research Group, School of Biological Sciences, University of Manchester, UK.
Int Immunol. 1996 Apr;8(4):559-67. doi: 10.1093/intimm/8.4.559.
In common with many intestinal nematode infections, Trichinella spiralis infections in mice are associated with a pronounced intestinal mast cell hyperplasia. The expulsion of the parasite from the gut is temporally associated with intestinal mastocytosis and mast cell function reflected by the secretion of mast cell protease into tissue and serum. In vivo, mucosal mast cell production is highly dependent upon T cell-derived cytokines including IL-3 and IL-4. We present data here to show that intestinal mast cell hyperplasia induced by helminth infection is also dependent upon the production of stem cell factor (SCF). Neutralization of SCF by anti-SCF or anti-SCF receptor mAb completely abrogated the mast cell hyperplasia generated by T. spiralis infection. Moreover, worm expulsion was dramatically delayed in treated mice and a reduced intestinal eosinophilia was observed. These effects did not appear to be mediated through alteration of Th cell responses and the parasite-specific serum antibody response was not affected. The reduction in the mast cell response and worm expulsion observed after SCF neutralization were reversible following cessation of monoclonal treatment. The data presented here clearly demonstrate a major role for SCF in the generation of intestinal mastocytosis and the host protective immune response following parasitic infection.
与许多肠道线虫感染一样，小鼠旋毛虫感染与明显的肠道肥大细胞增生有关。寄生虫从肠道排出在时间上与肠道肥大细胞增多症以及肥大细胞功能相关，肥大细胞功能通过肥大细胞蛋白酶分泌到组织和血清中得以体现。在体内，黏膜肥大细胞的产生高度依赖于T细胞衍生的细胞因子，包括白细胞介素-3和白细胞介素-4。我们在此展示的数据表明，蠕虫感染诱导的肠道肥大细胞增生也依赖于干细胞因子（SCF）的产生。用抗SCF或抗SCF受体单克隆抗体中和SCF可完全消除旋毛虫感染产生的肥大细胞增生。此外，治疗小鼠的蠕虫排出明显延迟，并且观察到肠道嗜酸性粒细胞增多减少。这些效应似乎不是通过改变Th细胞反应介导的，寄生虫特异性血清抗体反应也未受影响。在停止单克隆治疗后，SCF中和后观察到的肥大细胞反应和蠕虫排出的减少是可逆的。这里呈现的数据清楚地证明了SCF在寄生虫感染后肠道肥大细胞增多症的产生以及宿主保护性免疫反应中起主要作用。
