Futenma M, Kawakami K, Saito A
First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Microbiol Immunol. 1995;39(6):411-7. doi: 10.1111/j.1348-0421.1995.tb02221.x.
In the present study, a lethal model of pulmonary candidiasis was established using granulocytopenic mice with cyclophosphamide. These mice started to die 1 day after infection and had all died within the next 48 hr. The counts of live C. albicans in the lung gradually increased with time, while the organisms were quickly eliminated in the normal mice. From the histology and measurements on bronchoalveolar lavage fluid (BALF), polymorphonuclear cells (PMN) response was almost zero up to 24 hr; and then a weak but significant response was observed at 48 hr, while a marked accumulation of PMN was detected from as early as 6 hr in normal mice. In contrast, macrophages had accumulated in BALF by 48 hr in granulocytopenic mice, but not in normal mice. Both in serum and BALF, a considerable level of tumor necrosis factor-alpha (TNF-alpha) was detected from 6 hr, peaking at 24 to 48 hr, while in normal mice the quantity was under the detection limit in serum and very low in BALF. The effects of administering granulocyte colony-stimulating factor (G-CSF) on these parameters were next examined. G-CSF significantly prolonged the survival time of granulocytopenic mice, promoted the clearance of organisms through increasing the counts of PMN in the lung, and strongly inhibited the production of TNF-alpha both in BALF and serum. These results suggest that this cytokine does not protect them, but plays some role in their death due to candidial infection in granulocytopenic mice.
在本研究中，使用环磷酰胺诱导的粒细胞减少小鼠建立了肺部念珠菌病致死模型。这些小鼠在感染后1天开始死亡，并在接下来的48小时内全部死亡。肺中白色念珠菌的活菌计数随时间逐渐增加，而在正常小鼠中该菌很快被清除。从组织学和支气管肺泡灌洗液（BALF）检测结果来看，粒细胞减少小鼠在24小时内多形核细胞（PMN）反应几乎为零；然后在48小时观察到微弱但显著的反应，而正常小鼠早在6小时就检测到PMN明显聚集。相比之下，粒细胞减少小鼠在48小时时BALF中巨噬细胞已聚集，而正常小鼠则没有。在血清和BALF中，从6小时起就检测到相当水平的肿瘤坏死因子-α（TNF-α），在24至48小时达到峰值，而正常小鼠血清中的量低于检测限，BALF中的量非常低。接下来研究了给予粒细胞集落刺激因子（G-CSF）对这些参数的影响。G-CSF显著延长了粒细胞减少小鼠的存活时间，通过增加肺中PMN计数促进了菌的清除，并强烈抑制了BALF和血清中TNF-α的产生。这些结果表明，这种细胞因子并不能保护它们，而是在粒细胞减少小鼠因念珠菌感染导致的死亡中起了一定作用。
