Human alveolar macrophages are deficient in PTEN. The role of endogenous oxidants

Dawn M Flaherty; Martha M Monick; Sara L Hinde

doi:10.1074/jbc.M508997200

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Human alveolar macrophages are deficient in PTEN. The role of endogenous oxidants

Journal article

Open access

Peer reviewed

Human alveolar macrophages are deficient in PTEN. The role of endogenous oxidants

Dawn M Flaherty, Martha M Monick and Sara L Hinde

The Journal of biological chemistry, Vol.281(8), pp.5058-5064

02/24/2006

DOI: 10.1074/jbc.M508997200

PMID: 16371363

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Abstract

Human alveolar macrophages play a critical role in host defense and in the development of inflammation and fibrosis in the lung. Unlike their precursor cells, blood monocytes, alveolar macrophages are long-lived and tend to be resistant to apoptotic stimuli. In this study, we examined the role of differentiation in altering baseline phosphatidylinositol (PI) 3-kinase/Akt activity. We found that differentiation increased activity of pro-survival PI 3-kinase/Akt while decreasing amounts of the negative PI 3-kinase regulator, PTEN. PTEN is a lipid phosphatase with activity against phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3), the major bioactive product of PI 3-kinase. Examining in vivo differentiation of alveolar macrophages (by comparing blood monocytes to alveolar macrophages from single donors), we found that differentiation resulted in increased baseline reactive oxygen species (ROS) in the alveolar macrophages. This led to a deficiency in PTEN, increased activity of Akt, and prolonged survival of alveolar macrophages. These data support the hypothesis that alterations in ROS levels contribute to macrophage homeostasis by altering the balance between PI 3-kinase/Akt and the phosphatase, PTEN.

Oxidants - chemistry

Reactive Oxygen Species

Electron Spin Resonance Spectroscopy

Cell Survival

Down-Regulation

Humans

Cells, Cultured

Enzyme Inhibitors - pharmacology

Oxidants - metabolism

PTEN Phosphohydrolase - metabolism

Monocytes - metabolism

Phosphatidylinositol 3-Kinases - metabolism

RNA, Messenger - metabolism

Reverse Transcriptase Polymerase Chain Reaction

Blotting, Western

Macrophages - metabolism

Adenoviridae - genetics

Cell Differentiation

Lung - metabolism

Enzyme Activation

Macrophages, Alveolar - metabolism

Genetic Vectors

Proto-Oncogene Proteins c-akt - metabolism

Details

Title: Subtitle: Human alveolar macrophages are deficient in PTEN. The role of endogenous oxidants
Creators: Dawn M Flaherty - Division of Pulmonary, Critical Care and Occupational Medicine, Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, Iowa 52242, USA. dawn-flaherty@uiowa.edu
Martha M Monick
Sara L Hinde
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.281(8), pp.5058-5064
DOI: 10.1074/jbc.M508997200
PMID: 16371363
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Grant note: HL-60316 / NHLBI NIH HHS HL-077431 / NHLBI NIH HHS HL-04428 / NHLBI NIH HHS RR00059 / NCRR NIH HHS
Language: English
Date published: 02/24/2006
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
Record Identifier: 9984094736202771

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