Linked Life Data

17008602

Source:http://linkedlifedata.com/resource/pubmed/id/17008602

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2006-10-27
pubmed:abstractText
Heme toxicity contributes to the pathogenesis of chronic inflammatory diseases, atherosclerosis, and hemolysis associated vasculopathy. Macrophage clearance of cell free hemoglobin (Hb) is thus an essential homeostatic function of these cells. We examined the transcriptional response of human PBMC derived macrophages to Hb by gene array analysis. The observed noninflammatory macrophage response was characterized by induction of an antioxidative and antiinflammatory gene expression pattern with most prominent induction of the inducible heme oxygenase (HO-1). The metabolically active Hb-CD163-HO-1 pathway resulted in synthesis of ferritin-1 of the antioxidative and antiinflammatory end products linked to heme breakdown by HO-1. This response was mediated by the Hb scavenger receptor CD163 and heme and was not related to Hb mediated depletion of reduced glutathione. In contrast to other cellular responses induced by CD163, there was no role of protein phosphorylation dependent CD163 signaling in the protective macrophage response to Hb. Instead, CD163 acted as an Hb transporter, which undergoes constitutive and ligand independent internalization and recycling between the cell surface and early endosomes. The expression of CD163 and HO-1 in macrophages of neovascularized atherosclerotic lesions suggests that the pathway described herein is active in vivo. Noninflammatory Hb clearance and intimately linked HO-1 expression may provide the long sought-after explanation for the antiinflammatory activity associated with CD163-positive macrophages.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
27
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
943-50
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:17008602-Antigens, CD, pubmed-meshheading:17008602-Antigens, Differentiation, Myelomonocytic, pubmed-meshheading:17008602-Atherosclerosis, pubmed-meshheading:17008602-Cells, Cultured, pubmed-meshheading:17008602-Cytoprotection, pubmed-meshheading:17008602-Endocytosis, pubmed-meshheading:17008602-Endosomes, pubmed-meshheading:17008602-Gene Expression Profiling, pubmed-meshheading:17008602-Gene Expression Regulation, Enzymologic, pubmed-meshheading:17008602-Glutathione, pubmed-meshheading:17008602-Heme, pubmed-meshheading:17008602-Heme Oxygenase-1, pubmed-meshheading:17008602-Hemoglobins, pubmed-meshheading:17008602-Humans, pubmed-meshheading:17008602-Inflammation, pubmed-meshheading:17008602-Macrophages, pubmed-meshheading:17008602-Neovascularization, Pathologic, pubmed-meshheading:17008602-RNA, Messenger, pubmed-meshheading:17008602-Receptors, Cell Surface, pubmed-meshheading:17008602-Receptors, Scavenger, pubmed-meshheading:17008602-Transcription, Genetic
pubmed:year
2006
pubmed:articleTitle
Constitutive endocytosis of CD163 mediates hemoglobin-heme uptake and determines the noninflammatory and protective transcriptional response of macrophages to hemoglobin.
pubmed:affiliation
Department of Medicine, University Hospital, Zurich, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't