Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Blood |
| Vol/bind | 108 |
| Udgave nummer | 1 |
| Sider (fra-til) | 353-61 |
| Antal sider | 8 |
| ISSN | 0006-4971 |
| DOI | |
| Status | Udgivet - 2006 |
Bibliografisk note
Keywords: Cell Differentiation; Cytoplasmic Granules; Gene Expression Profiling; Granulocytes; Haptoglobins; Humans; Immunohistochemistry; Immunologic Deficiency Syndromes; Neutrophils; Reverse Transcriptase Polymerase Chain ReactionAdgang til dokumentet
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Haptoglobin is synthesized during granulocyte differentiation, stored in specific granules, and released by neutrophils in response to activation. / Theilgaard-Mönch, Kim; Jacobsen, Lars C; Nielsen, Marianne J; Rasmussen, Thomas; Udby, Lene; Gharib, Maged; Arkwright, Peter D; Gombart, Adrian F; Calafat, Jero; Moestrup, Søren K; Porse, Bo T; Borregaard, Niels.
I: Blood, Bind 108, Nr. 1, 2006, s. 353-61.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Haptoglobin is synthesized during granulocyte differentiation, stored in specific granules, and released by neutrophils in response to activation.
AU - Theilgaard-Mönch, Kim
AU - Jacobsen, Lars C
AU - Nielsen, Marianne J
AU - Rasmussen, Thomas
AU - Udby, Lene
AU - Gharib, Maged
AU - Arkwright, Peter D
AU - Gombart, Adrian F
AU - Calafat, Jero
AU - Moestrup, Søren K
AU - Porse, Bo T
AU - Borregaard, Niels
N1 - Keywords: Cell Differentiation; Cytoplasmic Granules; Gene Expression Profiling; Granulocytes; Haptoglobins; Humans; Immunohistochemistry; Immunologic Deficiency Syndromes; Neutrophils; Reverse Transcriptase Polymerase Chain Reaction
PY - 2006
Y1 - 2006
N2 - Haptoglobin (Hp) is a plasma protein synthesized primarily by hepatocytes. It exerts a broad range of anti-inflammatory activities and acts indirectly as a bacteriostatic agent and an antioxidant by virtue of its ability to bind free hemoglobin (Hb) and to facilitate its immediate clearance by macrophages. We identified Hp as a novel specific granule protein of neutrophils by means of immunoelectron microscopy, subcellular fractionation, and exocytosis studies. Consistent with these findings, blood cells from a patient with specific granule deficiency (SGD) lacked neutrophil-derived Hp. Neutrophils contained a large amount of highly glycosylated Hp (beta-chain 45-65 kDa) synthesized in neutrophil precursors and stored in specific granules and a small amount of Hp (beta-chain 39 kDa) endocytosed from plasma and stored in secretory vesicles. Subsequent binding studies revealed that Hp from specific granules binds to Hb. Finally, the CCAAT enhancer binding protein-epsilon (C/EBPepsilon) induced Hp transcription in a myeloid cell line, suggesting that Hp expression in myeloid cells, as in hepatocytes, is at least partially regulated by members of the C/EBP transcription factor family. Collectively, these findings demonstrate that Hp is stored in specific granules and is released by neutrophils in response to activation. Hence, neutrophil-derived Hp might reduce tissue damage and bacterial growth at sites of infection or injury by propagating anti-inflammatory activities and Hb clearance.
AB - Haptoglobin (Hp) is a plasma protein synthesized primarily by hepatocytes. It exerts a broad range of anti-inflammatory activities and acts indirectly as a bacteriostatic agent and an antioxidant by virtue of its ability to bind free hemoglobin (Hb) and to facilitate its immediate clearance by macrophages. We identified Hp as a novel specific granule protein of neutrophils by means of immunoelectron microscopy, subcellular fractionation, and exocytosis studies. Consistent with these findings, blood cells from a patient with specific granule deficiency (SGD) lacked neutrophil-derived Hp. Neutrophils contained a large amount of highly glycosylated Hp (beta-chain 45-65 kDa) synthesized in neutrophil precursors and stored in specific granules and a small amount of Hp (beta-chain 39 kDa) endocytosed from plasma and stored in secretory vesicles. Subsequent binding studies revealed that Hp from specific granules binds to Hb. Finally, the CCAAT enhancer binding protein-epsilon (C/EBPepsilon) induced Hp transcription in a myeloid cell line, suggesting that Hp expression in myeloid cells, as in hepatocytes, is at least partially regulated by members of the C/EBP transcription factor family. Collectively, these findings demonstrate that Hp is stored in specific granules and is released by neutrophils in response to activation. Hence, neutrophil-derived Hp might reduce tissue damage and bacterial growth at sites of infection or injury by propagating anti-inflammatory activities and Hb clearance.
U2 - 10.1182/blood-2005-09-3890
DO - 10.1182/blood-2005-09-3890
M3 - Journal article
C2 - 16543473
VL - 108
SP - 353
EP - 361
JO - Blood
JF - Blood
SN - 0006-4971
IS - 1
ER -