Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Schlager, S; Goeritzer, M; Jandl, K; Frei, R; Vujic, N; Kolb, D; Strohmaier, H; Dorow, J; Eichmann, TO; Rosenberger, A; Wölfler, A; Lass, A; Kershaw, EE; Ceglarek, U; Dichlberger, A; Heinemann, A; Kratky, D.
Adipose triglyceride lipase acts on neutrophil lipid droplets to regulate substrate availability for lipid mediator synthesis.
J Leukoc Biol. 2015; 98(5):837-50
Doi: 10.1189/jlb.3A0515-206R
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- Führende Autor*innen der Med Uni Graz
- Kratky Dagmar
- Schlager Stefanie
- Co-Autor*innen der Med Uni Graz
- Eichmann Thomas
- Frei-Winterleitner Robert
- Göritzer Madeleine
- Heinemann Akos
- Jandl Katharina
- Kolb Dagmar
- Schlacher Angelika
- Strohmaier Heimo
- Vujic Nemanja
- Wölfler Albert
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- Abstract:
- In humans, mutations in ATGL lead to TG accumulation in LDs of most tissues and cells, including peripheral blood leukocytes. This pathologic condition is called Jordans' anomaly, in which functional consequences have not been investigated. In the present study, we tested the hypothesis that ATGL plays a role in leukocyte LD metabolism and immune cell function. Similar to humans with loss-of-function mutations in ATGL, we found that global and myeloid-specific Atgl(-/-) mice exhibit Jordans' anomaly with increased abundance of intracellular TG-rich LDs in neutrophil granulocytes. In a model of inflammatory peritonitis, lipid accumulation was also observed in monocytes and macrophages but not in eosinophils or lymphocytes. Neutrophils from Atgl(-/-) mice showed enhanced immune responses in vitro, which were more prominent in cells from global compared with myeloid-specific Atgl(-/-) mice. Mechanistically, ATGL(-/-) as well as pharmacological inhibition of ATGL led to an impaired release of lipid mediators from neutrophils. These findings demonstrate that the release of lipid mediators is dependent on the liberation of precursor molecules from the TG-rich pool of LDs by ATGL. Our data provide mechanistic insights into Jordans' anomaly in neutrophils and suggest that ATGL is a potent regulator of immune cell function and inflammatory diseases.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Humans - administration & dosage
- Lipase - genetics, metabolism
- Lipid Droplets - enzymology, pathology
- Lipid Metabolism - administration & dosage
- Lipid Metabolism Disorders - enzymology, genetics, pathology
- Lymphocytes - enzymology, pathology
- Mice - administration & dosage
- Mice, Knockout - administration & dosage
- Monocytes - enzymology, pathology
- Neutrophils - enzymology, pathology
- Peritonitis - enzymology, genetics, pathology
- Find related publications in this database (Keywords)
- inflammatory cells
- arachidonic acid
- eicosanoids
- lipolysis