Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-44111
Vallelian, F; Schaer, C A; Kaempfer, T; Gehrig, P; Duerst, E; Schoedon, G; Schaer, D J (2010). Glucocorticoid treatment skews human monocyte differentiation into a hemoglobin-clearance phenotype with enhanced heme-iron recycling and antioxidant capacity. Blood, 116(24):5347-5356.
Glucocorticoids are used extensively to treat autoimmune hemolytic anemias. Some beneficial effects of glucocorticoid pulse therapy have also been reported in sickle cell disease and paroxysmal nocturnal hemoglobinuria. Based on established concepts of hemoglobin (Hb) toxicity and physiologic Hb scavenger systems, we evaluated whether glucocorticoids could support an adaptive response to extracellular Hb independently of their immunosuppressive activities. Using global proteome and transcriptome analysis with mass-spectrometry (isobaric tag for relative and absolute quantitation and liquid chromatography-mass spectrometry) and gene-array experiments, we found that glucocorticoid treatment in vitro and in patients on glucocorticoid-pulse therapy polarized monocytes into a M2/alternatively activated phenotype with high Hb-scavenger receptor (CD163) expression and enhanced Hb-clearance and detoxification capability. Monocytes concurrently exposed to the interactive activity of glucocorticoids and extracellular Hb were characterized by high expression of a group of antioxidant enzymes known to be regulated by the conserved oxidative response transcription factor nuclear factor E2-related factor. Further, suppressed transferrin receptor, together with high ferroportin expression, pointed to a shift in iron homeostasis directed toward an increased cellular export of heme-derived iron. Therefore, stimulating Hb-endocytosis by CD163 and enhancing antioxidative homeostasis and iron recycling may be an essential activity of glucocorticoids that helps alleviate the adverse effects of extracellular Hb.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic and Policlinic for Internal Medicine|
04 Faculty of Medicine > Functional Genomics Center Zurich
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||01 Feb 2011 12:11|
|Last Modified:||28 Nov 2013 00:34|
|Publisher:||American Society of Hematology|
|Additional Information:||This research was originally published in Blood.DOI: 10.1182/blood-2010-04-277319. Copyright by the American Society of Hematolog|
|Citations:||Web of Science®. Times Cited: 13|
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