ORCID
- Fejer, Gyorgy: 0000-0001-6761-0506
Abstract
AbstractThe enzyme tartrate resistant acid phosphatase (TRAP, two isoforms 5a and 5b) is highly expressed in alveolar macrophages, but its function there is unclear and potent selective inhibitors of TRAP are required to assess functional aspects of the protein. We found higher TRAP activity/expression in lungs of patients with chronic obstructive pulmonary disease (COPD) and asthma compared to controls and more TRAP activity in lungs of mice with experimental COPD or asthma. Stimuli related to asthma and/or COPD were tested for their capacity to induce TRAP. Receptor activator of NF-κb ligand (RANKL) and Xanthine/Xanthine Oxidase induced TRAP mRNA expression in mouse macrophages, but only RANKL also induced TRAP activity in mouse lung slices. Several Au(III) coordination compounds were tested for their ability to inhibit TRAP activity and [Au(4,4′-dimethoxy-2,2′-bipyridine)Cl2][PF6] (AubipyOMe) was found to be the most potent inhibitor of TRAP5a and 5b activity reported to date (IC50 1.3 and 1.8 μM respectively). AubipyOMe also inhibited TRAP activity in murine macrophage and human lung tissue extracts. In a functional assay with physiological TRAP substrate osteopontin, AubipyOMe inhibited mouse macrophage migration over osteopontin-coated membranes. In conclusion, higher TRAP expression/activity are associated with COPD and asthma and TRAP is involved in regulating macrophage migration.
DOI
10.1038/s41598-017-12623-w
Publication Date
2017-10-03
Publication Title
Scientific Reports
Volume
7
Issue
1
ISSN
2045-2322
Organisational Unit
School of Biomedical Sciences
Recommended Citation
Boorsma, C. E., van, d., Putri, K., de, A., Draijer, C., Mauad, T., Fejer, G., Brandsma, C., van, d., Bossé, Y., Sin, D., Hao, K., Reithmeier, A., Andersson, G., Olinga, P., Timens, W., Casini, A., & Melgert, B. (2017) 'A Potent Tartrate Resistant Acid Phosphatase Inhibitor to Study the Function of TRAP in Alveolar Macrophages', Scientific Reports, 7(1). Available at: https://doi.org/10.1038/s41598-017-12623-w
