| First Author | Xu L | Year | 2017 |
| Journal | Atherosclerosis | Volume | 263 |
| Pages | 42-52 | PubMed ID | 28600950 |
| Mgi Jnum | J:324637 | Mgi Id | MGI:6831989 |
| Doi | 10.1016/j.atherosclerosis.2017.05.024 | Citation | Xu L, et al. (2017) Histamine promotes the differentiation of macrophages from CD11b(+) myeloid cells and formation of foam cells through a Stat6-dependent pathway. Atherosclerosis 263:42-52 |
| abstractText | BACKGROUND AND AIMS: The enzyme histidine decarboxylase (Hdc), which generates histamine, is highly expressed in CD11b(+)Gr-1(+) myeloid cells that play a critical role in infection, inflammation and tumorigenesis. The aim of this study was to explore the role of Hdc-expressing CD11b(+) myeloid cells or histamine in atherogenesis. METHODS: Hdc-EGFP bacterial artificial chromosome (BAC) transgenic reporter mice (Hdc-EGFP) were used to track Hdc expression during the development of atherosclerosis. The expression of EGFP fluorescence was examined by immunofluorescence staining in a variety of adult tissues. Wild-type (WT), Apoe knockout (Apoe(-/-)), Hdc knockout (Hdc(-/-)), and Stat6 knockout (Stat6(-/-)) mice were used. Serum concentration of histamine was determined with ELISA. Changes in subsets of immune cells were evaluated by flow cytometry (FACS). Non-invasive tracking of the expression of CD11b(+) myeloid cells was tested using (125)I-anti-CD11b SPECT/CT imaging in the early stages of atherogenesis. Microarray analysis and RT-PCR were applied to detect gene expressions while Western blot was used to assess protein levels. RESULTS: Using Hdc-EGFP transgenic mice, we demonstrated that Hdc(+)CD11b(+) myeloid cells increase in the circulation in response to hypercholesterolemia and contribute to foam cell formation in atherosclerosis. Histamine deficiency in Hdc knockout (Hdc(-/-)) mice repressed the differentiation of CD11b(+)Ly6C(high) classically activated M1-type macrophages and CD11b(+)CD11c(+) dendritic cells (DCs), which was associated with downregulation of signal transducer and activator of transcription 6 (Stat6) expression. Furthermore, the results of in vivo and in vitro studies demonstrated that histamine could promote macrophage differentiation and foam cell formation via the Stat6 signal. CONCLUSIONS: Modulation of histamine and Stat6-signaling may represent an attractive therapeutic strategy for the prevention or treatment of atherosclerosis. |
