A potent tartrate resistant acid phosphatase inhibitor to study the function of TRAP in alveolar macrophages

Boorsma, Carian E., van der Veen, T. Anienke, Putri, Kurnia S. S., De Almeida, Andreia ORCID: https://orcid.org/0000-0002-6889-1503, Draijer, Christina, Mauad, Thais, Fejer, Gyorgy, Brandsma, Corry-Anke, van den Berge, Maarten, Bossé, Yohan, Sin, Don, Hao, Ke, Reithmeier, Anja, Andersson, Göran, Olinga, Peter, Timens, Wim, Casini, Angela ORCID: https://orcid.org/0000-0003-1599-9542 and Melgert, Barbro N. 2017. A potent tartrate resistant acid phosphatase inhibitor to study the function of TRAP in alveolar macrophages. Scientific Reports 7 (1) , 12570. 10.1038/s41598-017-12623-w

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Abstract

The 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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Chemistry
Publisher:	Nature Publishing Group: Open Access Journals - Option B / Nature Publishing Group
ISSN:	2045-2322
Date of First Compliant Deposit:	3 October 2017
Date of Acceptance:	13 September 2017
Last Modified:	03 May 2023 16:37
URI:	https://orca.cardiff.ac.uk/id/eprint/105141

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