Induction of fatty acid synthesis is a key requirement for phagocytic differentiation of human monocytes

Ecker, Josef and Liebisch, Gerhard and Englmaier, Marion and Grandl, Margot and Robenek, Horst and Schmitz, Gerd (2010) Induction of fatty acid synthesis is a key requirement for phagocytic differentiation of human monocytes. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 107 (17). pp. 7817-7822. ISSN 0027-8424,

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Abstract

Monocytes are precursors of macrophages. Here we demonstrate that macrophage colony-stimulating factor (M-CSF)-dependent differentiation of primary human monocytes from healthy volunteers induces transcription of SREBP-1c target genes required for fatty acid (FA) biosynthesis and impairs transcription of SREBP-2 target genes required for cholesterol synthesis. Detailed lipid metabolic profiling showed that this transcriptional regulation leads to a dramatically increased fatty acid synthesis as driving force for enhanced phospholipid synthesis. During cell differentiation the major lipid class switches from cholesterol in monocytes to phosphatidylcholine in macrophages. Ultrastructural analysis revealed that this transcriptional and metabolic regulation is essential for development of macrophage filopodia and cellular or-ganelles including primary lysosomes, endoplasmic reticulum, and Golgi network. Additional functional studies showed that suppression of fatty acid synthesis prevents phagocytosis representing a central macrophage function. Therefore induction of fatty acid synthesis is a key requirement for phagocyte development and function.

Item Type: Article
Uncontrolled Keywords: CTP-PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE; INSULIN-RESISTANCE; FREE-CHOLESTEROL; GENE-EXPRESSION; MACROPHAGES; MEMBRANE; ACTIVATION; SYNTHASE; DISEASE; CELLS; fatty acid metabolism; lipid mass spectrometry; phagocytes; phospholipid synthesis
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin
Depositing User: Dr. Gernot Deinzer
Date Deposited: 03 Aug 2020 06:02
Last Modified: 03 Aug 2020 06:02
URI: https://pred.uni-regensburg.de/id/eprint/24812

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