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J Biol Chem. 2018 Jul 20;293(29):11600-11611. doi: 10.1074/jbc.RA118.003180. Epub 2018 Jun 7.

Choline transport links macrophage phospholipid metabolism and inflammation.

Author information

1
From the University of Ottawa Centre for Infection, Immunity, and Inflammation and Centre for Catalysis Research and Innovation.
2
the Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
3
the Ottawa Institute of Systems Biology and University of Ottawa Brain and Mind Institute, and.
4
From the University of Ottawa Centre for Infection, Immunity, and Inflammation and Centre for Catalysis Research and Innovation, morgan.fullerton@uottawa.ca.

Abstract

Choline is an essential nutrient that is required for synthesis of the main eukaryote phospholipid, phosphatidylcholine. Macrophages are innate immune cells that survey and respond to danger and damage signals. Although it is well-known that energy metabolism can dictate macrophage function, little is known as to the importance of choline homeostasis in macrophage biology. We hypothesized that the uptake and metabolism of choline are important for macrophage inflammation. Polarization of primary bone marrow macrophages with lipopolysaccharide (LPS) resulted in an increased rate of choline uptake and higher levels of PC synthesis. This was attributed to a substantial increase in the transcript and protein expression of the choline transporter-like protein-1 (CTL1) in polarized cells. We next sought to determine the importance of choline uptake and CTL1 for macrophage immune responsiveness. Chronic pharmacological or CTL1 antibody-mediated inhibition of choline uptake resulted in altered cytokine secretion in response to LPS, which was associated with increased levels of diacylglycerol and activation of protein kinase C. These experiments establish a previously unappreciated link between choline phospholipid metabolism and macrophage immune responsiveness, highlighting a critical and regulatory role for macrophage choline uptake via the CTL1 transporter.

KEYWORDS:

CTL1/Slc44a1; choline; choline transport; de novo lipogenesis; inflammation; macrophage; phosphatidylcholine; phospholipid

PMID:
29880645
PMCID:
PMC6065184
DOI:
10.1074/jbc.RA118.003180
[Indexed for MEDLINE]
Free PMC Article

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