PMID- 25339664
OWN - NLM
STAT- MEDLINE
DCOM- 20150416
LR  - 20211021
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 193
IP  - 11
DP  - 2014 Dec 1
TI  - ABCG1 is required for pulmonary B-1 B cell and natural antibody homeostasis.
PG  - 5637-48
LID - 10.4049/jimmunol.1400606 [doi]
AB  - Many metabolic diseases, including atherosclerosis, type 2 diabetes, pulmonary 
      alveolar proteinosis, and obesity, have a chronic inflammatory component 
      involving both innate and adaptive immunity. Mice lacking the ATP-binding 
      cassette transporter G1 (ABCG1) develop chronic inflammation in the lungs, which 
      is associated with the lipid accumulation (cholesterol, cholesterol ester, and 
      phospholipid) and cholesterol crystal deposition that are characteristic of 
      atherosclerotic lesions and pulmonary alveolar proteinosis. In this article, we 
      demonstrate that specific lipids, likely oxidized phospholipids and/or sterols, 
      elicit a lung-specific immune response in Abcg1(-/-) mice. Loss of ABCG1 results 
      in increased levels of specific oxysterols, phosphatidylcholines, and oxidized 
      phospholipids, including 
      1-palmitoyl-2-(5'-oxovaleroyl)-sn-glycero-3-phosphocholine, in the lungs. 
      Further, we identify a niche-specific increase in natural Ab (NAb)-secreting B-1 
      B cells in response to this lipid accumulation that is paralleled by increased 
      titers of IgM, IgA, and IgG against oxidation-specific epitopes, such as those on 
      oxidized low-density lipoprotein and malondialdehyde-modified low-density 
      lipoprotein. Finally, we identify a cytokine/chemokine signature that is 
      reflective of increased B cell activation, Ab secretion, and homing. 
      Collectively, these data demonstrate that the accumulation of lipids in 
      Abcg1(-/-) mice induces the specific expansion and localization of B-1 B cells, 
      which secrete NAbs that may help to protect against the development of 
      atherosclerosis. Indeed, despite chronic lipid accumulation and inflammation, 
      hyperlipidemic mice lacking ABCG1 develop smaller atherosclerotic lesions 
      compared with controls. These data also suggest that Abcg1(-/-) mice may 
      represent a new model in which to study the protective functions of B-1 B 
      cells/NAbs and suggest novel targets for pharmacologic intervention and treatment 
      of disease.
CI  - Copyright (c) 2014 by The American Association of Immunologists, Inc.
FAU - Baldan, Angel
AU  - Baldan A
AD  - Division of Cardiology, Department of Medicine, David Geffen School of Medicine, 
      University of California Los Angeles, Los Angeles, CA 90095; Edward A. Doisy 
      Department of Biochemistry and Molecular Biology, St. Louis University, St. 
      Louis, MO 63104;
FAU - Gonen, Ayelet
AU  - Gonen A
AD  - Department of Medicine, University of California San Diego, La Jolla, CA 92093;
FAU - Choung, Christina
AU  - Choung C
AD  - Division of Cardiology, Department of Medicine, David Geffen School of Medicine, 
      University of California Los Angeles, Los Angeles, CA 90095;
FAU - Que, Xuchu
AU  - Que X
AD  - Department of Medicine, University of California San Diego, La Jolla, CA 92093;
FAU - Marquart, Tyler J
AU  - Marquart TJ
AD  - Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis 
      University, St. Louis, MO 63104;
FAU - Hernandez, Irene
AU  - Hernandez I
AD  - Instituto de Investigaciones Biomedicas "Alberto Sols" Consejo Superior de 
      Investigaciones Cientificas - Universidad Autonoma de Madrid, Madrid 28006; 
      Unidad Asociada de Biomedicina IIBM-Universidad de Las Palmas de Gran Canaria, 
      Las Palmas 35016, Spain; and.
FAU - Bjorkhem, Ingemar
AU  - Bjorkhem I
AD  - Karolinska Institutet, Stockholm 11 171, Sweden.
FAU - Ford, David A
AU  - Ford DA
AD  - Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis 
      University, St. Louis, MO 63104;
FAU - Witztum, Joseph L
AU  - Witztum JL
AD  - Department of Medicine, University of California San Diego, La Jolla, CA 92093;
FAU - Tarling, Elizabeth J
AU  - Tarling EJ
AD  - Division of Cardiology, Department of Medicine, David Geffen School of Medicine, 
      University of California Los Angeles, Los Angeles, CA 90095; 
      ETarling@mednet.ucla.edu.
LA  - eng
GR  - P01 HL088093/HL/NHLBI NIH HHS/United States
GR  - R21 HL111906/HL/NHLBI NIH HHS/United States
GR  - HL088093/HL/NHLBI NIH HHS/United States
GR  - U54 GM069338/GM/NIGMS NIH HHS/United States
GR  - HL074214/HL/NHLBI NIH HHS/United States
GR  - K99 HL118161/HL/NHLBI NIH HHS/United States
GR  - R01 HL107794/HL/NHLBI NIH HHS/United States
GR  - R01 HL074214/HL/NHLBI NIH HHS/United States
GR  - HL107794/HL/NHLBI NIH HHS/United States
GR  - GM69338-06/GM/NIGMS NIH HHS/United States
GR  - R00 HL118161/HL/NHLBI NIH HHS/United States
GR  - HL111906/HL/NHLBI NIH HHS/United States
GR  - P01 HL030568/HL/NHLBI NIH HHS/United States
GR  - HL118161/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141022
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 (Antibodies)
RN  - 0 (Avian Proteins)
RN  - 0 (Cytokines)
RN  - 0 (EMF-1 protein, Gallus gallus)
RN  - 0 (Lipoproteins)
RN  - 0 (Phospholipids)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1
MH  - ATP-Binding Cassette Transporters/genetics/*metabolism
MH  - Adoptive Transfer
MH  - Animals
MH  - Antibodies/metabolism
MH  - Atherosclerosis/*immunology
MH  - Avian Proteins/metabolism
MH  - B-Lymphocyte Subsets/*immunology/transplantation
MH  - B-Lymphocytes/*immunology/transplantation
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Gene Expression Profiling
MH  - Homeostasis/genetics
MH  - Lipid Metabolism, Inborn Errors/genetics
MH  - Lipoproteins/genetics/*metabolism
MH  - Lung/immunology/*metabolism
MH  - Lymphocyte Activation
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Oxidation-Reduction
MH  - Phospholipids/metabolism
PMC - PMC4239162
MID - NIHMS631711
COIS- Disclosures The authors have no conflicts of interest or disclosures. J.L.W. and 
      X.Q. have patents and disclosures related to the use of oxidation-specific 
      antibodies, which are owned by the University of California San Diego.
EDAT- 2014/10/24 06:00
MHDA- 2015/04/17 06:00
PMCR- 2015/12/01
CRDT- 2014/10/24 06:00
PHST- 2014/10/24 06:00 [entrez]
PHST- 2014/10/24 06:00 [pubmed]
PHST- 2015/04/17 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - jimmunol.1400606 [pii]
AID - 10.4049/jimmunol.1400606 [doi]
PST - ppublish
SO  - J Immunol. 2014 Dec 1;193(11):5637-48. doi: 10.4049/jimmunol.1400606. Epub 2014 
      Oct 22.