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SHR Neuro Cancer Cardio Lipid Metab Microb
Buerger, M; Amor, M; Akhmetshina, A; Bianco, V; Perfler, B; Zebisch, A; Weichhart, T; Kratky, D.
Limited Alleviation of Lysosomal Acid Lipase Deficiency by Deletion of Matrix Metalloproteinase 12.
Int J Mol Sci. 2024; 25(20): 11001
Doi: 10.3390/ijms252011001
[OPEN ACCESS]
Web of Science
PubMed
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FullText_MUG
- Leading authors Med Uni Graz
- Bürger Martin
- Kratky Dagmar
- Co-authors Med Uni Graz
- Akhmetshina Alena
- Amor Melina
- Bianco Valentina
- Perfler Bianca
- Zebisch Armin
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- Abstract:
- Lysosomal acid lipase (LAL) is the only known enzyme that degrades cholesteryl esters and triglycerides at an acidic pH. In LAL deficiency (LAL-D), dysregulated expression of matrix metalloproteinase 12 (MMP-12) has been described. The overexpression of MMP-12 in myeloid lineage cells causes an immune cell dysfunction resembling that of Lal knockout (Lal KO) mice. Both models develop progressive lymphocyte dysfunction and expansion of myeloid-derived suppressor (CD11b+ Gr-1+) cells. To study whether MMP-12 might be a detrimental contributor to the pathology of LAL-D, we have generated Lal/Mmp12 double knockout (DKO) mice. The phenotype of Lal/Mmp12 DKO mice closely resembled that of Lal KO mice, while the weight and morphology of the thymus were improved in Lal/Mmp12 DKO mice. Cytological examination of blood smears showed a mildly reversed lymphoid-to-myeloid shift in DKO mice. Despite significant decreases in CD11b+ Ly6G+ cells in the peripheral blood, bone marrow, and spleen of Lal/Mmp12 DKO mice, the hematopoietic bone marrow progenitor compartment and markers for neutrophil chemotaxis were unchanged. Since the overall severity of LAL-D remains unaffected by the deletion of Mmp12, we conclude that MMP-12 does not represent a viable target for treating the inflammatory pathology in LAL-D.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Matrix Metalloproteinase 12 - genetics, metabolism
- Mice, Knockout - administration & dosage
- Mice - administration & dosage
- Sterol Esterase - genetics, deficiency, metabolism
- Wolman Disease - genetics, pathology
- CD11b Antigen - metabolism
- Disease Models, Animal - administration & dosage
- Neutrophils - metabolism
- Mice, Inbred C57BL - administration & dosage
- Gene Deletion - administration & dosage
- Find related publications in this database (Keywords)
- LAL
- lysosomal storage disease
- matrix metalloproteinase 12
- CD11b+Ly6G+cells
- myeloid-derived suppressor cells
- lymphoid-to-myeloid shift
- chronic inflammation