PMID- 21036914
OWN - NLM
STAT- MEDLINE
DCOM- 20110128
LR  - 20200930
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Linking)
VI  - 300
IP  - 1
DP  - 2011 Jan
TI  - Restoration of PPARgamma reverses lipid accumulation in alveolar macrophages of 
      GM-CSF knockout mice.
PG  - L73-80
LID - 10.1152/ajplung.00128.2010 [doi]
AB  - Pulmonary alveolar proteinosis (PAP) is a lung disease characterized by a 
      deficiency of functional granulocyte macrophage colony-stimulating factor 
      (GM-CSF) resulting in surfactant accumulation and lipid-engorged alveolar 
      macrophages. GM-CSF is a positive regulator of PPARgamma that is constitutively 
      expressed in healthy alveolar macrophages. We previously reported decreased PPARgamma 
      and ATP-binding cassette transporter G1 (ABCG1) levels in alveolar macrophages 
      from PAP patients and GM-CSF knockout (KO) mice, suggesting PPARgamma and ABCG1 
      involvement in surfactant catabolism. Because ABCG1 represents a PPARgamma target, we 
      hypothesized that PPARgamma restoration would increase ABCG1 and reduce macrophage 
      lipid accumulation. Upregulation of PPARgamma was achieved using a lentivirus 
      expression system in vivo. GM-CSF KO mice received intratracheal instillation of 
      lentivirus (lenti)-PPARgamma or control lenti-eGFP. Ten days postinstillation, 79% of 
      harvested alveolar macrophages expressed eGFP, demonstrating transduction. 
      Alveolar macrophages showed increased PPARgamma and ABCG1 expression after 
      lenti-PPARgamma instillation, whereas PPARgamma and ABCG1 levels remained unchanged in 
      lenti-eGFP controls. Alveolar macrophages from lenti-PPARgamma-treated mice also 
      exhibited reduced intracellular phospholipids and increased cholesterol efflux to 
      HDL, an ABCG1-mediated pathway. In vivo instillation of lenti-PPARgamma results in: 
      1) upregulating ABCG1 and PPARgamma expression of GM-CSF KO alveolar macrophages, 2) 
      reducing intracellular lipid accumulation, and 3) increasing cholesterol efflux 
      activity.
FAU - Malur, Anagha
AU  - Malur A
AD  - East Carolina Univ., Greenville, NC 27834, USA.
FAU - Baker, Anna D
AU  - Baker AD
FAU - McCoy, Almedia J
AU  - McCoy AJ
FAU - Wells, Greg
AU  - Wells G
FAU - Barna, Barbara P
AU  - Barna BP
FAU - Kavuru, Mani S
AU  - Kavuru MS
FAU - Malur, Achut G
AU  - Malur AG
FAU - Thomassen, Mary Jane
AU  - Thomassen MJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101029
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (ABCG1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Lipids)
RN  - 0 (PPAR gamma)
RN  - 0 (Pulmonary Surfactants)
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/metabolism
MH  - Animals
MH  - Cholesterol/metabolism
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/deficiency/*genetics/physiology
MH  - Humans
MH  - Lipids/physiology
MH  - Macrophages, Alveolar/metabolism/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - PPAR gamma/*genetics/metabolism/therapeutic use
MH  - Pulmonary Alveolar Proteinosis/drug therapy/genetics/metabolism
MH  - Pulmonary Surfactants/metabolism
EDAT- 2010/11/03 06:00
MHDA- 2011/02/01 06:00
CRDT- 2010/11/02 06:00
PHST- 2010/11/02 06:00 [entrez]
PHST- 2010/11/03 06:00 [pubmed]
PHST- 2011/02/01 06:00 [medline]
AID - ajplung.00128.2010 [pii]
AID - 10.1152/ajplung.00128.2010 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2011 Jan;300(1):L73-80. doi: 
      10.1152/ajplung.00128.2010. Epub 2010 Oct 29.