| Online-Ressource |
Verfasst von: | Gleißner, Christian A. [VerfasserIn]  |
| Shaked, Iftach [VerfasserIn]  |
| Erbel, Christian [VerfasserIn]  |
| Böckler, Dittmar [VerfasserIn]  |
| Katus, Hugo [VerfasserIn]  |
| Ley, Klaus [VerfasserIn]  |
Titel: | CXCL4 downregulates the atheroprotective hemoglobin receptor CD163 in human macrophages |
Verf.angabe: | Christian A. Gleissner, Iftach Shaked, Christian Erbel, Dittmar Böckler, Hugo A. Katus, and Klaus Ley |
E-Jahr: | 2010 |
Jahr: | 2010 January 8 |
Umfang: | 19 S. |
Fussnoten: | Das PDF umfasst 19 Seiten ; Gesehen am 03.04.2023 |
Titel Quelle: | Enthalten in: Journal of banking and finance |
Ort Quelle: | Amsterdam : Elsevier North-Holland, 1977 |
Jahr Quelle: | 2010 |
Band/Heft Quelle: | 106(2010), 1, Seite 203-211 |
ISSN Quelle: | 1872-6372 |
Abstract: | 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. |
DOI: | doi:10.1161/CIRCRESAHA.109.199505 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
DOI: https://doi.org/10.1161/CIRCRESAHA.109.199505 |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | Animals |
| Antigens, CD |
| Antigens, Differentiation, Myelomonocytic |
| Apolipoproteins E |
| Atherosclerosis |
| Cell Differentiation |
| Gene Expression Regulation |
| Heme Oxygenase-1 |
| Hemoglobins |
| Humans |
| Macrophages |
| Mice |
| Mice, Knockout |
| Monocytes |
| Platelet Factor 4 |
| Receptors, Cell Surface |
| Receptors, Scavenger |
K10plus-PPN: | 1841074292 |
Verknüpfungen: | → Zeitschrift |
CXCL4 downregulates the atheroprotective hemoglobin receptor CD163 in human macrophages / Gleißner, Christian A. [VerfasserIn]; 2010 January 8 (Online-Ressource)