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

Research output: Contribution to journalArticle

31 Citations (Scopus)

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

Fingerprint

Pneumocystis Pneumonia
Alveolar Macrophages
Polyamines
Bronchoalveolar Lavage Fluid
Apoptosis
Fluids
Pneumocystis
Animals
Chemical activation
Pneumocystis Infections
Spermidine
Caspase 9
DNA Fragmentation
Cytochromes c
Metabolism
Caspase 3
Rats
Reactive Oxygen Species
Cytoplasm
Lung

ASJC Scopus subject areas

  • Biochemistry

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

Polyamine-mediated apoptosis of alveolar macrophages during Pneumocystis pneumonia. / Lasbury, Mark E.; Merali, Salim; Durant, Pamela J.; Tschang, Dennis; Ray, Chad A.; Lee, Chao-Hung.

In: Journal of Biological Chemistry, Vol. 282, No. 15, 13.04.2007, p. 11009-11020.

Research output: Contribution to journalArticle

Lasbury, ME, Merali, S, Durant, PJ, Tschang, D, Ray, CA & Lee, C-H 2007, 'Polyamine-mediated apoptosis of alveolar macrophages during Pneumocystis pneumonia', Journal of Biological Chemistry, vol. 282, no. 15, pp. 11009-11020. https://doi.org/10.1074/jbc.M611686200
Lasbury, Mark E. ; Merali, Salim ; Durant, Pamela J. ; Tschang, Dennis ; Ray, Chad A. ; Lee, Chao-Hung. / Polyamine-mediated apoptosis of alveolar macrophages during Pneumocystis pneumonia. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 15. pp. 11009-11020.
@article{d169fd5cf1a54cae978fb27c507a60e0,
title = "Polyamine-mediated apoptosis of alveolar macrophages during Pneumocystis pneumonia",
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.",
author = "Lasbury, {Mark E.} and Salim Merali and Durant, {Pamela J.} and Dennis Tschang and Ray, {Chad A.} and Chao-Hung Lee",
year = "2007",
month = "4",
day = "13",
doi = "10.1074/jbc.M611686200",
language = "English",
volume = "282",
pages = "11009--11020",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "15",

}

TY - JOUR

T1 - Polyamine-mediated apoptosis of alveolar macrophages during Pneumocystis pneumonia

AU - Lasbury, Mark E.

AU - Merali, Salim

AU - Durant, Pamela J.

AU - Tschang, Dennis

AU - Ray, Chad A.

AU - Lee, Chao-Hung

PY - 2007/4/13

Y1 - 2007/4/13

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34249729916&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34249729916&partnerID=8YFLogxK

U2 - 10.1074/jbc.M611686200

DO - 10.1074/jbc.M611686200

M3 - Article

C2 - 17314093

AN - SCOPUS:34249729916

VL - 282

SP - 11009

EP - 11020

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 15

ER -