PMID- 22033401
OWN - NLM
STAT- MEDLINE
DCOM- 20120118
LR  - 20181201
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 415
IP  - 2
DP  - 2011 Nov 18
TI  - Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung 
      compliance in GM-CSF knock-out mice.
PG  - 288-93
LID - 10.1016/j.bbrc.2011.10.043 [doi]
AB  - We have shown decreased expression of the nuclear transcription factor, 
      peroxisome proliferator-activated receptor-gamma (PPARgamma) and the PPARgamma-regulated 
      ATP-binding cassette transporter G1 (ABCG1) in alveolar macrophages from patients 
      with pulmonary alveolar proteinosis (PAP). PAP patients also exhibit neutralizing 
      antibodies to granulocyte-macrophage colony stimulating factor (GM-CSF), an 
      upregulator of PPARgamma. In association with functional GM-CSF deficiency, PAP lung 
      is characterized by surfactant-filled alveolar spaces and lipid-filled alveolar 
      macrophages. Similar pathology characterizes GM-CSF knock-out (KO) mice. We 
      reported previously that intratracheal instillation of a lentivirus (lenti)-PPARgamma 
      plasmid into GM-CSF KO animals elevated ABCG1 and reduced alveolar macrophage 
      lipid accumulation. Here, we hypothesized that instillation of lenti-ABCG1 might 
      be sufficient to decrease lipid accumulation and improve pulmonary function in 
      GM-CSF KO mice. Animals received intratracheal instillation of lenti-ABCG1 or 
      control lenti-enhanced Green Fluorescent Protein (eGFP) plasmids and alveolar 
      macrophages were harvested 10 days later. Alveolar macrophage transduction 
      efficiency was 79% as shown by lenti-eGFP fluorescence. Quantitative PCR analyses 
      indicated a threefold (p=0.0005) increase in ABCG1 expression with no change of 
      PPARgamma or ABCA1 in alveolar macrophages of lenti-ABCG1 treated mice. ABCG1 was 
      unchanged in control lenti-eGFP and PBS-instilled groups. Oil Red O staining 
      detected reduced intracellular neutral lipid in alveolar macrophages from 
      lenti-ABCG1 treated mice. Extracellular cholesterol and phospholipids were also 
      decreased as shown by analysis of bronchoalveolar lavage fluid. Lung compliance 
      was diminished in untreated GMCSF KO mice but improved significantly after 
      lenti-ABCG1 treatment. Data demonstrate that in vivo instillation of lenti-ABCG1 
      in GM-CSF KO mice is sufficient to restore pulmonary homeostasis by: (1) 
      upregulating ABCG1; (2) reducing intra and extracellular lipids; and (3) 
      improving lung function. Results suggest that the ABCG1 lipid transporter is the 
      key downstream target of GM-CSF-induced PPARgamma necessary for surfactant 
      catabolism.
CI  - Published by Elsevier Inc.
FAU - Malur, Anagha
AU  - Malur A
AD  - Program in Lung Cell Biology and Translational Research, Division of Pulmonary, 
      Critical Care and Sleep Medicine, East Carolina University, Greenville, NC 27834, 
      United States.
FAU - Huizar, Isham
AU  - Huizar I
FAU - Wells, Greg
AU  - Wells G
FAU - Barna, Barbara P
AU  - Barna BP
FAU - Malur, Achut G
AU  - Malur AG
FAU - Thomassen, Mary Jane
AU  - Thomassen MJ
LA  - eng
PT  - Journal Article
DEP - 20111018
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (ABCG1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Phospholipids)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1
MH  - ATP-Binding Cassette Transporters/*genetics
MH  - Animals
MH  - Cholesterol/*metabolism
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/*genetics
MH  - Humans
MH  - Lentivirus
MH  - Lung/metabolism/*physiology
MH  - Macrophages, Alveolar/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Phospholipids/*metabolism
MH  - Up-Regulation
EDAT- 2011/10/29 06:00
MHDA- 2012/01/19 06:00
CRDT- 2011/10/29 06:00
PHST- 2011/09/20 00:00 [received]
PHST- 2011/10/10 00:00 [accepted]
PHST- 2011/10/29 06:00 [entrez]
PHST- 2011/10/29 06:00 [pubmed]
PHST- 2012/01/19 06:00 [medline]
AID - S0006-291X(11)01840-7 [pii]
AID - 10.1016/j.bbrc.2011.10.043 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2011 Nov 18;415(2):288-93. doi: 
      10.1016/j.bbrc.2011.10.043. Epub 2011 Oct 18.