1. ATP-binding cassette transporter hallmarks tissue macrophages and modulates cytokine-triggered polarization programs.
- Author
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Pradel LC, Mitchell AJ, Zarubica A, Dufort L, Chasson L, Naquet P, Broccardo C, and Chimini G
- Subjects
- ATP Binding Cassette Transporter 1, ATP-Binding Cassette Transporters genetics, Animals, Bacterial Proteins genetics, Bacterial Proteins metabolism, Blotting, Western, Cells, Cultured, Cyclooxygenase 2 metabolism, Flow Cytometry, Gene Expression Profiling, HeLa Cells, Humans, Immunophenotyping, Interferon-gamma pharmacology, Interleukin-4 pharmacology, Luminescent Proteins genetics, Luminescent Proteins metabolism, Macrophages cytology, Macrophages metabolism, Macrophages, Peritoneal cytology, Macrophages, Peritoneal drug effects, Macrophages, Peritoneal metabolism, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Knockout, Phosphorylation drug effects, Reverse Transcriptase Polymerase Chain Reaction, STAT1 Transcription Factor metabolism, Species Specificity, ATP-Binding Cassette Transporters metabolism, Cytokines pharmacology, Macrophages drug effects
- Abstract
Macrophages are central players in both lipid metabolism and innate immunity. Their determinant role in the pathogenesis of atherosclerosis is under the control of the ATP-binding cassette transporter (ABCA1), which by minimizing cellular lipid content, limits development of pro-inflammatory foam cells. Considering the differential contribution of monocyte subsets to the generation of vascular lesions we analyzed the immunophenotype of ABCA1-expressing cells in the myeloid lineage, by the combined use of flow cytometry and real-time quantitative RT-PCR. ABCA1 expression is limited to "non-inflammatory" Ly6C(lo) circulating monocytes and tissue-resident macrophages expressing markers of alternative activation. In ABCA1(-/-) peritoneal macrophages the transcriptional programs induced by LPS/IFN-gamma or IL-4 cytokines are altered and deviated phosphorylation patterns of STAT transcriptional regulators in response to stimuli are observed.
- Published
- 2009
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