4.3 Article

Lysosomal lipid hydrolysis provides substrates for lipid mediator synthesis in murine macrophages

期刊

ONCOTARGET
卷 8, 期 25, 页码 40037-40051

出版社

IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.16673

关键词

lysosomal acid lipase; LAL-D; lysosome; eicosanoids; lipid mediator; Immunology and Microbiology Section; Immune response; Immunity

资金

  1. Austrian Science Fund FWF [DK-MCD W1226, DK-MOLIN W1241, P27070]
  2. BioTechMed-Graz flagship project Lipid Signaling
  3. PhD program 'Molecular Medicine' of the Medical University of Graz
  4. Austrian Science Fund (FWF) [P27070] Funding Source: Austrian Science Fund (FWF)

向作者/读者索取更多资源

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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.3
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据