Identification of an autophagy defect in smokers' alveolar macrophages

Martha M Monick; Linda S Powers; Katherine Walters; Nina Lovan; Michael Zhang; Alicia Gerke; Sif Hansdottir; Gary W Hunninghake

doi:10.4049/jimmunol.1001603

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Identification of an autophagy defect in smokers' alveolar macrophages

Journal article

Peer reviewed

Identification of an autophagy defect in smokers' alveolar macrophages

Martha M Monick, Linda S Powers, Katherine Walters, Nina Lovan, Michael Zhang, Alicia Gerke, Sif Hansdottir and Gary W Hunninghake

The Journal of immunology (1950), Vol.185(9), pp.5425-5435

11/01/2010

DOI: 10.4049/jimmunol.1001603

PMCID: PMC3057181

PMID: 20921532

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Abstract

Alveolar macrophages are essential for clearing bacteria from the alveolar surface and preventing microbe-induced infections. It is well documented that smokers have an increased incidence of infections, in particular lung infections. Alveolar macrophages accumulate in smokers' lungs, but they have a functional immune deficit. In this study, we identify an autophagy defect in smokers' alveolar macrophages. Smokers' alveolar macrophages accumulate both autophagosomes and p62, a marker of autophagic flux. The decrease in the process of autophagy leads to impaired protein aggregate clearance, dysfunctional mitochondria, and defective delivery of bacteria to lysosomes. This study identifies the autophagy pathway as a potential target for interventions designed to decrease infection rates in smokers and possibly in individuals with high environmental particulate exposure.

Smoking - adverse effects

Microscopy, Electron, Transmission

Macrophages, Alveolar - pathology

Smoking - immunology

Humans

Phagosomes - metabolism

Phagosomes - pathology

Blotting, Western

Autophagy - immunology

Phagosomes - immunology

Transfection

Smoking - pathology

Macrophages, Alveolar - metabolism

Macrophages, Alveolar - immunology

Microscopy, Fluorescence

Details

Title: Subtitle: Identification of an autophagy defect in smokers' alveolar macrophages
Creators: Martha M Monick - Department of Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. martha-monick@uiowa.edu
Linda S Powers
Katherine Walters
Nina Lovan
Michael Zhang
Alicia Gerke
Sif Hansdottir
Gary W Hunninghake
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.185(9), pp.5425-5435
DOI: 10.4049/jimmunol.1001603
PMID: 20921532
PMCID: PMC3057181
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: R01 HL096625 / NHLBI NIH HHS UL1 RR024979 / NCRR NIH HHS R01 HL077431 / NHLBI NIH HHS R01 HL096625-01A1 / NHLBI NIH HHS UL1RR024979 / NCRR NIH HHS R01 HL079901 / NHLBI NIH HHS
Language: English
Date published: 11/01/2010
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
Record Identifier: 9984094586202771

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