Polyamine-mediated apoptosis of alveolar macrophages during Pneumocystis pneumonia.
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.
Lasbury
Mark E
ME
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. melasbur@iupui.edu
Merali
Salim
S
Durant
Pamela J
PJ
Tschang
Dennis
D
Ray
Chad A
CA
Lee
Chao-Hung
CH
D000107:Acetylation; D000818:Animals; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002452:Cell Count; D002875:Chromosomes / Q000235:genetics; D004247:DNA / Q000235:genetics; D004789:Enzyme Activation; D005260:Female; D016676:Macrophages, Alveolar / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D011020:Pneumonia, Pneumocystis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D011073:Polyamines; D017382:Reactive Oxygen Species; D004247:DNA; D053148:Caspase 3; D053453:Caspase 9