Polyamine-mediated apoptosis of alveolar macrophages during Pneumocystis pneumonia

Mark E. Lasbury, Salim Merali, Pamela J. Durant, Dennis Tschang, Chad A. Ray, Chao Hung Lee

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)11009-11020
Number of pages12
JournalJournal of Biological Chemistry
Volume282
Issue number15
DOIs
StatePublished - Apr 13 2007

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lasbury, M. E., Merali, S., Durant, P. J., Tschang, D., Ray, C. A., & Lee, C. H. (2007). Polyamine-mediated apoptosis of alveolar macrophages during Pneumocystis pneumonia. Journal of Biological Chemistry, 282(15), 11009-11020. https://doi.org/10.1074/jbc.M611686200