ArticleThe American journal of pathology2010
Critical roles of lysosomal acid lipase in myelopoiesis.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 43 citations in OpenAlex.
- Low lysosomal acid lipase activity is associated with histological progression of metabolic dysfunction-associated steatotic liver disease.Hepatology international · 2026Article
- Rescue of lysosomal acid lipase deficiency in mice by rAAV8 liver gene transfer.Communications medicine · 2025Article
- Lysosomes in the immunometabolic reprogramming of immune cells in atherosclerosis.Nature reviews. Cardiology · 2025Review
- LAL deficiency induced myeloid-derived suppressor cells as targets and biomarkers for lung cancer.Journal for immunotherapy of cancer · 2023Article
- Lysosomal Acid Lipase Deficiency: Genetics, Screening, and Preclinical Study.International journal of molecular sciences · 2022Review
- Review
- Lysosomal acid lipase, CSF1R, and PD-L1 determine functions of CD11c+ myeloid-derived suppressor cells.JCI insight · 2022Article
- Enzyme replacement therapy and hematopoietic stem cell transplant: a new paradigm of treatment in Wolman disease.Orphanet journal of rare diseases · 2021Article
- Effect of Lipids and Lipoproteins on Hematopoietic Cell Metabolism and Commitment in Atherosclerosis.Immunometabolism · 2021Article
- Lysosomal Acid Lipase Deficiency Controls T- and B-Regulatory Cell Homeostasis in the Lymph Nodes of Mice with Human Cancer Xenotransplants.The American journal of pathology · 2021Article
- Lysosomal Acid Lipase Is Required for Donor T Cells to Induce Graft-versus-Host Disease.Cell reports · 2020Article
- Fat for fuel: lipid metabolism in haematopoiesis.Clinical & translational immunology · 2019Review
- Myeloid-Derived Suppressor Cells and Their Potential Application in Transplantation.Transplantation · 2018Review
- Endothelial Rab7 GTPase mediates tumor growth and metastasis in lysosomal acid lipase-deficient mice.The Journal of biological chemistry · 2017Article
- Autophagy-Dependent Generation of Free Fatty Acids Is Critical for Normal Neutrophil Differentiation.Immunity · 2017Article
- Lysosomal lipid hydrolysis provides substrates for lipid mediator synthesis in murine macrophages.Oncotarget · 2017Article
- Rab7 GTPase controls lipid metabolic signaling in myeloid-derived suppressor cells.Oncotarget · 2017Article
- Lysosomal acid lipase in mesenchymal stem cell stimulation of tumor growth and metastasis.Oncotarget · 2016Article
- Lung Epithelial Cell-Specific Expression of Human Lysosomal Acid Lipase Ameliorates Lung Inflammation and Tumor Metastasis in Lipa(-/-) Mice.The American journal of pathology · 2016Article
- Critical role of PPARγ in myeloid-derived suppressor cell-stimulated cancer cell proliferation and metastasis.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Lysosomal acid lipase (LAL) is a key enzyme that cleaves cholesteryl esters and triglycerides to generate free fatty acids and cholesterol in lysosomes. Genetic ablation of the lal gene (lal(-/-)) in mice has resulted in a systemic increase of macrophages and neutrophils, causing severe inflammation and pathogenesis in multiple organs. We hypothesized that aberrant growth and differentiation of myeloid cells in lal(-/-) mice arises from dysregulated production of progenitor cells in the bone marrow. Indeed, lal(-/-) mice displayed increased numbers of primitive lin(-)Sca-1(+)c-Kit(+) (LSK) cells and granulocyte-macrophage precursors (GMP). Increased high proliferative potential colony-forming cells (HPP-CFC) were enumerated from cultured lal(-/-) bone marrow cells, as were significantly more CFU-GM, CFU-G, and CFU-M colonies. As a consequence, lal(-/-) mice developed significant myeloid infiltration, particularly with CD11b+/Gr-1+ myeloid-derived suppressive cells in multiple organs. Both decreased apoptosis and increased proliferation contribute to the systemic increase of myeloid cells in lal(-/-) myeloid cells. These lal(-/-) CD11b(+)/Gr-1(+) cells displayed suppressive activity on T cell proliferation and function in vitro. Bone marrow chimeras confirmed that the myeloproliferative disorder in lal(-/-) mice was primarily attributable to autonomous defects in myeloid progenitor cells, although the hematopoietic microenvironment in the lal(-/-) mice did not support hematopoiesis normally. These results provide evidence that LAL is an important regulator of myelopoiesis during hematopoietic development, differentiation, and homeostasis.
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Registered trials
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