Abd A H, Savage N W, Halliday W J, Hume D A
Department of Microbiology, University of Queensland, St. Lucia, Brisbane, Australia.
Lymphokine Cytokine Res. 1991 Apr;10(1-2):43-50.
Intraperitoneal injection of Streptococcus agalactiae sonicated cells into Wistar rats causes a chronic relapsing polyarthritis resembling human rheumatoid arthritis. We report evidence favoring a role for macrophages in the pathology of this disease. S. agalactiae injected ip induced a high level of tumor necrosis factor release by peritoneal macrophages isolated subsequently, and had a similar effect when added to control peritoneal macrophages in culture. Ia antigen was induced on macrophages in both the peritoneum and affected joints following S. agalactiae injection. The role of macrophages in the disease process was studied by treating animals prior to S. agalactiae injection with varying concentrations of bacterial lipopolysaccharide (LPS), silica, and carrageenan, agents known to have a biphasic effect on macrophage function. They aggravated the pathology at low doses but prevented the disease at high doses. The most specific alteration of macrophage levels was achieved by injection of recombinant human macrophage colony-stimulating factor (CSF-1). Treatment with CSF-1 early in the disease lead to significant worsening of the pathology. Administration of CSF-1 after 2 weeks reactivated the disease and extended the chronic phase. These data in combination with previous findings are consistent with nonimmune, macrophage-mediated pathology for this model of arthritis. The results have implications for therapeutic application of CSF-1.
向Wistar大鼠腹腔注射无乳链球菌超声破碎细胞会引发一种类似于人类类风湿性关节炎的慢性复发性多关节炎。我们报告了支持巨噬细胞在该疾病病理过程中起作用的证据。腹腔注射无乳链球菌可诱导随后分离出的腹腔巨噬细胞释放高水平的肿瘤坏死因子，并且在培养中添加到对照腹腔巨噬细胞时也有类似效果。注射无乳链球菌后，腹膜和受累关节中的巨噬细胞均诱导产生Ia抗原。通过在注射无乳链球菌之前用不同浓度的细菌脂多糖（LPS）、二氧化硅和角叉菜胶处理动物来研究巨噬细胞在疾病过程中的作用，已知这些试剂对巨噬细胞功能具有双相作用。它们在低剂量时会加重病理状况，但在高剂量时可预防疾病。通过注射重组人巨噬细胞集落刺激因子（CSF-1）可实现巨噬细胞水平最特异性的改变。在疾病早期用CSF-1治疗会导致病理状况明显恶化。在2周后给予CSF-1可使疾病重新激活并延长慢性期。这些数据与先前的研究结果相结合，与该关节炎模型的非免疫性、巨噬细胞介导的病理过程一致。这些结果对CSF-1的治疗应用具有启示意义。
