CXCL4 downregulates the atheroprotective hemoglobin receptor CD163 in human macrophages
RATIONALE: CXCL4 is a platelet-derived chemokine that promotes macrophage differentiation from monocytes. Deletion of the PF4 gene that encodes CXCL4 reduces atherosclerotic lesions in ApoE(-/-) mice. - OBJECTIVE: We sought to study effects of CXCL4 on macrophage differentiation with possible releva...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2010 January 8
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| In: |
Journal of banking and finance
Year: 2010, Volume: 106, Issue: 1, Pages: 203-211 |
| ISSN: | 1872-6372 |
| Online Access: |
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| Author Notes: | Christian A. Gleissner, Iftach Shaked, Christian Erbel, Dittmar Böckler, Hugo A. Katus, and Klaus Ley |
| Summary: | RATIONALE: CXCL4 is a platelet-derived chemokine that promotes macrophage differentiation from monocytes. Deletion of the PF4 gene that encodes CXCL4 reduces atherosclerotic lesions in ApoE(-/-) mice. - OBJECTIVE: We sought to study effects of CXCL4 on macrophage differentiation with possible relevance for atherogenesis. - METHODS AND RESULTS: Flow cytometry for expression of surface markers in macrophage colony-stimulating factor (M-CSF)- and CXCL4-induced macrophages demonstrated virtually complete absence of the hemoglobin scavenger receptor CD163 in CXCL4-induced macrophages. mRNA for CD163 was downregulated as early as 2 hours after CXCL4. CD163 protein reached a minimum after 3 days, which was not reversed by treatment of cells with M-CSF. The CXCL4 effect was entirely neutralized by heparin, which bound CXCL4 and prevented CXCL4 surface binding to monocytes. Pretreatment of cells with chlorate, which inhibits glycosaminoglycan synthesis, strongly inhibited CXCL4-dependent downregulation of CD163. Similar to recombinant CXCL4, releasate from human platelets also reduced CD163 expression. CXCL4-differentiated macrophages were unable to upregulate the atheroprotective enzyme heme oxygenase-1 at the RNA and protein level in response to hemoglobin-haptoglobin complexes. Immunofluorescence of human atherosclerotic plaques demonstrated presence of both CD68+CD163+ and CD68+CD163- macrophages. PF4 and CD163 gene expression within human atherosclerotic lesions were inversely correlated, supporting the in vivo relevance of CXCL4-induced downregulation of CD163. - CONCLUSIONS: CXCL4 may promote atherogenesis by suppressing CD163 in macrophages, which are then unable to upregulate the atheroprotective enzyme heme oxygenase-1 in response to hemoglobin. |
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| Item Description: | Das PDF umfasst 19 Seiten Gesehen am 03.04.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1872-6372 |