Dang-Vu A P, Pisetsky D S, Weinberg J B
J Immunol. 1987 Mar 15;138(6):1757-61.
To assess the role of macrophages (MAC) in the pathogenesis of systemic lupus erythematosus, we investigated functional aspects of peritoneal MAC obtained from autoimmune MRL/MpJ-lpr/lpr (MRL-lpr) mice. MRL-lpr and control C3H/HeN MAC were obtained from untreated mice or mice injected i.p. with 1 ml of 10% sterile peptone 3 days before cell harvest. MRL-lpr mice had significantly more peritoneal cells (MAC and lymphocytes) than did control mice. In endotoxin-free conditions, MRL-lpr MAC were similar to C3H/HeN MAC in their baseline, and IFN-gamma and/or LPS enhanced cytolysis of 3T12 fibrosarcoma tumor cells. Compared with C3H/HeN MAC, MRL-lpr MAC had a significant increase in antibody-dependent cellular cytotoxicity activity against sheep erythrocytes. This enhanced activity was not accompanied by a similar increase in adherence and/or phagocytosis of the same targets. Finally, in response to phorbol myristate acetate stimulation, both resident and peptone-induced MAC from MRL-lpr mice produced significantly more hydrogen peroxide than did those from control mice. These results indicate that MAC from MRL-lpr mice display features of selective "activation", and suggest that MAC or their products may play a role in the pathogenesis of inflammatory disorders seen in autoimmune diseases.
为了评估巨噬细胞(MAC)在系统性红斑狼疮发病机制中的作用,我们研究了从自身免疫性MRL/MpJ-lpr/lpr(MRL-lpr)小鼠获得的腹腔MAC的功能特性。MRL-lpr和对照C3H/HeN MAC来自未处理的小鼠或在细胞收获前3天腹腔注射1 ml 10%无菌蛋白胨的小鼠。MRL-lpr小鼠的腹腔细胞(MAC和淋巴细胞)明显多于对照小鼠。在无内毒素条件下,MRL-lpr MAC在基线时与C3H/HeN MAC相似,并且IFN-γ和/或LPS增强了3T12纤维肉瘤肿瘤细胞的细胞溶解作用。与C3H/HeN MAC相比,MRL-lpr MAC对绵羊红细胞的抗体依赖性细胞毒性活性显著增加。这种增强的活性并没有伴随着对相同靶标的黏附和/或吞噬作用的类似增加。最后,在佛波酯肉豆蔻酸酯乙酸盐刺激下,来自MRL-lpr小鼠的驻留型和蛋白胨诱导型MAC产生的过氧化氢均明显多于对照小鼠。这些结果表明,来自MRL-lpr小鼠的MAC表现出选择性“激活”的特征,并提示MAC或其产物可能在自身免疫性疾病中所见的炎症性疾病的发病机制中起作用。