Lasbury Mark E, Merali Salim, Durant Pamela J, Tschang Dennis, Ray Chad A, Lee Chao-Hung
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
J Biol Chem. 2007 Apr 13;282(15):11009-20. doi: 10.1074/jbc.M611686200. Epub 2007 Feb 21.
The number of alveolar macrophages is decreased during Pneumocystis pneumonia (Pcp), partly because of activation of apoptosis in these cells. This apoptosis occurs in both rat and mouse models of Pcp. Bronchoalveolar lavage (BAL) fluids from Pneumocystis-infected animals were found to contain high levels of polyamines, including spermidine, N1-acetylspermine, and N1-acetylspermidine. These BAL fluids and exogenous polyamines were able to induce apoptosis in alveolar macrophages. Apoptosis of alveolar macrophages during infection, after incubation with BAL fluids from Pneumocystis-infected animals, or after incubation with polyamines was marked by an increase in intracellular reactive oxygen species, activation of caspases-3 and -9, DNA fragmentation, and leakage of mitochondrial cytochrome c into the cytoplasm. When polyamines were depleted from the BAL fluids of infected animals, the ability of these BAL fluids to induce apoptosis was lost. Interestingly, the apoptosis inducing activity of the polyamine-depleted BAL fluids was restored when polyamines were added back. The results of this study suggested that Pneumocystis infection results in accumulation of high levels of polyamines in the lung. These polyamines activate apoptosis of alveolar macrophages, perhaps because of the ROS that are produced during polyamine metabolism.
在肺孢子菌肺炎（Pcp）期间，肺泡巨噬细胞数量减少，部分原因是这些细胞中凋亡被激活。这种凋亡在Pcp的大鼠和小鼠模型中均会发生。发现来自感染肺孢子菌动物的支气管肺泡灌洗（BAL）液中含有高水平的多胺，包括亚精胺、N1 - 乙酰精胺和N1 - 乙酰亚精胺。这些BAL液和外源性多胺能够诱导肺泡巨噬细胞凋亡。感染期间、与来自感染肺孢子菌动物的BAL液孵育后或与多胺孵育后，肺泡巨噬细胞的凋亡表现为细胞内活性氧增加、半胱天冬酶 - 3和 - 9激活、DNA片段化以及线粒体细胞色素c泄漏到细胞质中。当从感染动物的BAL液中去除多胺时，这些BAL液诱导凋亡的能力丧失。有趣的是，当重新添加多胺时，去除多胺的BAL液的凋亡诱导活性得以恢复。这项研究的结果表明，肺孢子菌感染导致肺中高水平多胺的积累。这些多胺激活肺泡巨噬细胞的凋亡，可能是由于多胺代谢过程中产生的活性氧。
