PMID- 18322240
OWN - NLM
STAT- MEDLINE
DCOM- 20080610
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 180
IP  - 6
DP  - 2008 Mar 15
TI  - A critical role for ABCG1 in macrophage inflammation and lung homeostasis.
PG  - 4273-82
AB  - ATP-binding cassette transporter G1 (ABCG1) effluxes cholesterol from macrophages 
      and plays an important role in pulmonary lipid homeostasis. We hypothesize that 
      macrophages from Abcg1(-/-) mice have increased inflammatory activity, thereby 
      promoting acceleration of pulmonary disease. We herein demonstrate increased 
      numbers of inflammatory cytokines and infiltrating neutrophils, eosinophils, 
      dendritic cells, T cells, and B cells into lungs of Abcg1(-/-) mice before the 
      onset of severe lipidosis. We further investigated the role of macrophages in 
      causing pulmonary disease by performing bone marrow transplantations using B6 and 
      Abcg1(-/-) bone marrow. We found that it was the macrophage, and not pneumocyte 
      type II cells or other nonhematopoietic cells in the lung, that appeared to be 
      the primary cell type involved in the onset of both pulmonary lipidosis and 
      inflammation in the Abcg1(-/-) mice. Additionally, our results demonstrate that 
      Abcg1(-/-) macrophages had elevated proinflammatory cytokine production, 
      increased apoptotic cell clearance, and were themselves more prone to apoptosis 
      and necrosis. However, they were quickly repopulated by monocytes that were 
      recruited to Abcg1(-/-) lungs. In conclusion, we have shown that ABCG1 deletion 
      in macrophages causes a striking inflammatory phenotype and initiates onset of 
      pulmonary lipidosis in mice. Thus, our studies reveal a critical role for 
      macrophage ABCG1 in lung inflammation and homeostasis.
FAU - Wojcik, Allison J
AU  - Wojcik AJ
AD  - Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, 
      USA.
FAU - Skaflen, Marcus D
AU  - Skaflen MD
FAU - Srinivasan, Suseela
AU  - Srinivasan S
FAU - Hedrick, Catherine C
AU  - Hedrick CC
LA  - eng
GR  - P0I HL55798/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (ABCG1 protein, mouse)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipoproteins)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1
MH  - ATP-Binding Cassette Transporters/genetics/*physiology
MH  - Animals
MH  - Animals, Newborn
MH  - Homeostasis/genetics/*immunology
MH  - Humans
MH  - Inflammation Mediators/metabolism/*physiology
MH  - Jurkat Cells
MH  - Lipid Metabolism/genetics/immunology
MH  - Lipoproteins/deficiency/genetics/*physiology
MH  - Lung/cytology/*immunology/metabolism/*pathology
MH  - Macrophages/*immunology/metabolism/*pathology
MH  - Macrophages, Alveolar/immunology/metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
EDAT- 2008/03/07 09:00
MHDA- 2008/06/11 09:00
CRDT- 2008/03/07 09:00
PHST- 2008/03/07 09:00 [pubmed]
PHST- 2008/06/11 09:00 [medline]
PHST- 2008/03/07 09:00 [entrez]
AID - 180/6/4273 [pii]
AID - 10.4049/jimmunol.180.6.4273 [doi]
PST - ppublish
SO  - J Immunol. 2008 Mar 15;180(6):4273-82. doi: 10.4049/jimmunol.180.6.4273.