Human ATP-binding cassette transporter TaqMan low-density array: analysis of macrophage differentiation and foam cell formation
Open accessAbstract
Background: ATP-binding cassette (ABC) transporters cause various diseases and regulate many physiologic processes, such as lipid homeostasis, iron transport, and immune mechanisms. Several ABC transporters are involved in bile acid, phospholipid, and sterol transport, and their expression is itself controlled by lipids. In addition, ABC proteins mediate drug export in tumor cells and promote the development of multidrug resistance. Methods: We created an ABC Transporter TaqMan Low-Density Array based on an Applied Biosystems 7900HT Micro Fluidic Card. We used a 2-μL reaction well with 2 ng of sample. To evaluate this method for lipidomic research and to characterize expression patterns of ABC transporters in cells relevant for atherosclerosis research, we monitored mRNA expression in human primary monocytes, in vitro–differentiated macrophages, and cells stimulated with the liver-X-receptor and retinoid-X-receptor agonists T0901317 and 9-cis retinoic acid, mimicking sterol loading. Results: The method enabled simultaneous analysis of 47 human ABC transporters and the reference gene 18S rRNA in 2 replicates of 4 samples per run. Conclusions: The new system uses only 2 ng of sample and small volumes of reagent, and the precaptured primers and probes avoided labor-intensive pipetting steps. The ABC Transporter TaqMan Low-Density Array may be a useful tool to monitor dysregulated ABC transporter mRNA profiles in human lipid disorders and cancer-related multidrug resistance and to analyze the pharmacologic and metabolic regulation of ABC transporter expression important for drug development in large-scale screening approaches.
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Primary human monocytes/macrophages virtually lack ABCD2 gene expression.
“In contrast to primary mouse peritoneal macrophages, primary human monocytes/macrophages virtually lack ABCD2 gene expression [40], [41].”
From Abcd2 Is a Strong Modifier of the Metabolic Impairments in Peritoneal Macrophages of Abcd1-Deficient Mice (2014) · cites this paper as [40]
The Results say that 30 ABC transporters had detectable mRNA in human primary monocytes and refer to Table 1, but the passages available from our copy do not identify ABCD2 as expressed or unexpressed. Searches for ABCD2 and for its absence in monocytes/macrophages found no gene-specific result; the Table 1 passage contains only its caption and notes. (LLM, conf=0.72)
Experimental — accuracy not yet measuredIn human monocytes/macrophages, ABCD2 is virtually not expressed and therefore cannot compensate for the functional loss of ABCD1, resulting in a severe metabolic phenotype in this cell lineage of X-ALD patients.
“In human monocytes/macrophages, ABCD2 is virtually not expressed [40] and, therefore, cannot compensate for the functional loss of ABCD1 resulting in a severe metabolic phenotype in this cell lineage of X-ALD patients [41].”
From Abcd2 Is a Strong Modifier of the Metabolic Impairments in Peritoneal Macrophages of Abcd1-Deficient Mice (2014) · cites this paper as [40]
The cited paper’s Table 1 caption describes ABC-transporter expression measurements in monocytes and macrophages, but the passages available in our copy do not give an ABCD2 result. Searches for “ABCD2” and its expression in these cells found no passage establishing that it is virtually unexpressed. The compensation and X-ALD phenotype statement is attached to a different citation, [41]. (LLM, conf=0.72)
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Cites
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“In contrast to primary mouse peritoneal macrophages, primary human monocytes/macrophages virtually lack ABCD2 gene expression [40,41].”
Background
- Authors
- Langmann, T., Mauerer, R., & Schmitz, G.
- Affiliations
- University of Regensburg (DE)
- Corresponding author
- Langmann, Thomas
- Venue
- Clinical Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-02-01
- Volume
- 52
- Issue
- 2
- Pages
- 310-313
- ISSN
- 0009-9147 (ISSN-L)
- 1530-8561
- OpenAlex
- W2154758696
- Cited by
- 49
- References
- 8
- Citations by year
- 2026: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2015: 3 · 2014: 2 · 2013: 5 · 2012: 2
- FWCI
- 7.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Clinical Chemistry (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
- University of Regensburg Publication Server (University of Regensburg)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- ABC transporters, TaqMan Low Density Array, macrophage differentiation, foam cell formation, atherosclerosis, lipidomics, mRNA expression profiling, liver X receptor agonist, T0901317, 9-cis-retinoic acid, monocytes, multidrug resistance, lipid metabolism disorders
- MeSH terms
- Cell Differentiation, Cells, Cultured, Foam Cells, Humans, Leukocytes, Mononuclear, Macrophages, Polymerase Chain Reaction, ATP-Binding Cassette Transporters, Taq Polymerase
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