Wyler D J, Stadecker M J, Dinarello C A, O'Dea J F
J Immunol. 1984 Jun;132(6):3142-8.
Isolated intact egg granulomas from the liver of Schistosoma mansoni-infected mice have been previously shown to elaborate factors in vitro that can stimulate fibroblasts for biological functions that are of potential importance in the pathogenesis of hepatic fibrosis in schistosomiasis. We report here that cell cultures obtained from monodispersed granuloma cell suspensions, and specifically enriched for macrophages (95% to 100%) spontaneously elaborated fibroblast proliferation-stimulating activity in vitro. These cells possessed functional and phenotyptic characteristics of activated macrophages. In contrast, control peritoneal macrophages from uninfected mice lacked such phenotypic characteristics, and did not spontaneously elaborate fibrogenic activity in vitro. The granuloma macrophage activity was present, pre-formed within the isolated cells, and was continuously elaborated during 72 hr of incubation. By gel infiltration chromatography (Sephacryl S-200 sf), fibroblast-stimulating activity was identified in two pooled fractions, one with estimated molecular radius (Mr) of 46 kd to 57 kd and the other with Mr of 10 kd to 16 kd. Preparative isoelectric focusing in granular gel of crude macrophage culture supernatants identified peak activity in fractions with pI approximately 5. Two different serine esterase inhibitors had no effect on the ability of crude granuloma macrophage supernatants to stimulate fibroblast proliferation. Whereas crude and chromatographed fractions of granuloma macrophage supernatant were active for fibroblasts, they had minimal or no interleukin 1 (IL 1) activity when tested in a thymocyte proliferation assay. In contrast, resident peritoneal macrophages from the same infected mice spontaneously secreted substantial IL 1 and fibroblast-stimulating activity in vitro. We conclude that egg granuloma macrophages are activated in vivo to secrete fibrogenic molecules functionally distinct from IL 1, which might contribute to the pathogenesis of hepatic fibrosis in schistosomiasis.
此前已证明，从感染曼氏血吸虫的小鼠肝脏中分离出的完整虫卵肉芽肿，在体外能产生一些因子，这些因子可刺激成纤维细胞发挥生物学功能，而这些功能在血吸虫病肝纤维化的发病机制中可能具有潜在重要性。我们在此报告，从单分散的肉芽肿细胞悬液中获得的细胞培养物，特别是富含巨噬细胞（95%至100%）的培养物，在体外能自发产生刺激成纤维细胞增殖的活性。这些细胞具有活化巨噬细胞的功能和表型特征。相比之下，未感染小鼠的对照腹腔巨噬细胞缺乏此类表型特征，在体外也不会自发产生促纤维化活性。肉芽肿巨噬细胞活性在分离出的细胞内预先形成，并在孵育72小时期间持续产生。通过凝胶渗透色谱法（Sephacryl S - 200 sf），在两个合并的组分中鉴定出了刺激成纤维细胞的活性，一个组分的估计分子半径（Mr）为46 kd至57 kd，另一个组分的Mr为10 kd至16 kd。在颗粒凝胶中对粗制巨噬细胞培养上清液进行制备性等电聚焦，在pI约为5的组分中鉴定出峰值活性。两种不同的丝氨酸酯酶抑制剂对粗制肉芽肿巨噬细胞上清液刺激成纤维细胞增殖的能力没有影响。虽然肉芽肿巨噬细胞上清液的粗制品和经色谱分离的组分对成纤维细胞有活性，但在胸腺细胞增殖试验中检测时，它们的白细胞介素1（IL - 1）活性极小或没有。相比之下，来自相同感染小鼠的驻留腹腔巨噬细胞在体外能自发分泌大量的IL - 1和刺激成纤维细胞的活性。我们得出结论，虫卵肉芽肿巨噬细胞在体内被激活，以分泌功能上不同于IL - 1的促纤维化分子，这可能有助于血吸虫病肝纤维化的发病机制。
