A phagocytic cell line markedly improves survival of infected neutropenic mice
A phagocytic cell line markedly improves survival of infected neutropenic mice
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DOI：
10.1189/jlb.0205072
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发表时间：
2005-08-01
影响因子：
5.5
通讯作者：
Ibrahim, AS
中科院分区：
文献类型：
--
作者：
Spellberg, BJ;Collins, M;Ibrahim, AS
播散性念珠菌病是一种常见的感染性疾病，尽管有抗真菌治疗，但仍有50%的患者死亡。由于中性粒细胞减少的持续时间是侵袭性真菌感染的血小板减少患者生存的最强预测因子，中性粒细胞输注是一种合理的治疗选择。然而，重大的技术障碍阻碍了中性粒细胞输注的临床应用。为了克服这些障碍，我们确定了一种人吞噬细胞系，可以代替新鲜收获的中性粒细胞给予念珠菌宿主。HL-60细胞在体外对白色念珠菌有杀伤作用。用二甲基亚砜和维甲酸激活HL-60细胞，抑制细胞增殖，增强细胞对C.白色念珠菌将活化的HL-60细胞给予念珠菌病、血小板减少的小鼠显著改善了存活率（53% vs. 0%）。活HL-60细胞趋化至感染部位，吞噬C.白色念珠菌，并减少了关键靶器官中的真菌负荷。虽然未活化的HL-60细胞也降低了体内组织真菌负荷，但由于其在感染小鼠中的毒性，它们并没有改善存活率。相比之下，在长达2个月的随访中未观察到活化HL-60细胞导致的毒性。据我们所知，这是第一次描述基于细胞系的感染性疾病免疫疗法。随着进一步的改进，活化的HL-60细胞有可能克服中性粒细胞输注的技术障碍。
Disseminated candidiasis is a frequent infection in neutropenic patients, in whom it causes 50% mortality, despite antifungal therapy. As the duration of neutropenia is the strongest predictor of survival in neutropenic patients with invasive fungal infections, neutrophil transfusions are a logical, therapeutic option. However, significant technical barriers have prevented the clinical use of neutrophil transfusions. To overcome these barriers, we identified a human phagocytic cell line that could be administered to candidemic hosts in lieu of freshly harvested neutrophils. HL-60 cells killed Candida albicans in vitro. Activation of HL-60 cells with dimethyl sulfoxide and retinoic acid abrogated the cells' proliferation and augmented their killing of C. albicans. Administration of activated HL-60 cells to candidemic, neutropenic mice significantly improved survival (53% vs. 0%). Live HL-60 cells chemotaxed to sites of infection, phagocytized C. albicans, and reduced the fungal burden in key target organs. Although unactivated HL-60 cells also reduced tissue fungal burden in vivo, they did not improve survival as a result of their toxicity in infected mice. In contrast, no toxicity as a result of activated HL-60 cells was observed at up to 2 months of follow-up. To our knowledge, this is the first description of a cell line-based immunotherapy for an infectious disease. With further refinements, activated HL-60 cells have the potential to overcome the technical barriers to neutrophil transfusions.