Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Schlager, S; Vujic, N; Korbelius, M; Duta-Mare, M; Dorow, J; Leopold, C; Rainer, S; Wegscheider, M; Reicher, H; Ceglarek, U; Sattler, W; Radovic, B; Kratky, D.
Lysosomal lipid hydrolysis provides substrates for lipid mediator synthesis in murine macrophages.
Oncotarget. 2017; 8(25):40037-40051
Doi: 10.18632/oncotarget.16673
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- Führende Autor*innen der Med Uni Graz
- Kratky Dagmar
- Schlager Stefanie
- Co-Autor*innen der Med Uni Graz
- Duta-Mare Madalina-Cristina
- Hinteregger Helga
- Korbelius Melanie
- Leopold Christina
- Radovic Branislav
- Rainer Silvia
- Sattler Wolfgang
- Vujic Nemanja
- Wegscheider Martin
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- Abstract:
- Degradation of lysosomal lipids requires lysosomal acid lipase (LAL), the only intracellular lipase known to be active at acidic pH. We found LAL to be expressed in murine immune cells with highest mRNA expression in macrophages and neutrophils. Furthermore, we observed that loss of LAL in mice caused lipid accumulation in white blood cells in the peripheral circulation, which increased in response to an acute inflammatory stimulus. Lal-deficient (-/-) macrophages accumulate neutral lipids, mainly cholesteryl esters, within lysosomes. The cholesteryl ester fraction is particularly enriched in the PUFAs 18:2 and 20:4, important precursor molecules for lipid mediator synthesis. To investigate whether loss of LAL activity affects the generation of lipid mediators and to eliminate potential systemic effects from other cells and tissues involved in the pronounced phenotype of Lal-/- mice, we treated macrophages from Wt mice with the LAL-specific inhibitor LAListat-2. Acute inhibition of LAL resulted in reduced release of 18:2- and 20:4-derived mediators from macrophages, indicating that lipid hydrolysis by LAL is an important source for lipid mediator synthesis in macrophages. We conclude that lysosomes should be considered as organelles that provide precursor molecules for lipid mediators such as eicosanoids.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Carbamates - pharmacology
- Cholesterol Esters - metabolism
- Eicosanoids - metabolism
- Female -
- Hydrolysis -
- Lipid Metabolism -
- Lipids - analysis
- Lipids - blood
- Lysosomes - metabolism
- Macrophages - drug effects
- Macrophages - metabolism
- Male -
- Mice, Inbred C57BL -
- Mice, Knockout -
- Sterol Esterase - antagonists & inhibitors
- Sterol Esterase - genetics
- Sterol Esterase - metabolism
- Substrate Specificity -
- Thiadiazoles - pharmacology
- Find related publications in this database (Keywords)
- lysosomal acid lipase
- LAL-D
- lysosome
- eicosanoids
- lipid mediator
- Immunology and Microbiology Section
- Immune response
- Immunity