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Verfasst von:Gleißner, Christian A. [VerfasserIn]   i
 Shaked, Iftach [VerfasserIn]   i
 Erbel, Christian [VerfasserIn]   i
 Böckler, Dittmar [VerfasserIn]   i
 Katus, Hugo [VerfasserIn]   i
 Ley, Klaus [VerfasserIn]   i
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

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