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Serpina1 is a potent inhibitor of IL-8-induced hematopoietic stem cell mobilization
- Source :
- Proceedings of the National Academy of Sciences of the United States of America, 103(5), 1469-1474. NATL ACAD SCIENCES
- Publication Year :
- 2006
- Publisher :
- NATL ACAD SCIENCES, 2006.
-
Abstract
- Here, we report that cytokine-induced (granulocyte colony-stimulating factor and IL-8) hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) mobilization is completely inhibited after low-dose (0.5 Gy) total-body irradiation (TBI). Because neutrophil granular proteases are regulatory mediators in cytokine-induced HSC/HPC mobilization, we considered a possible role for protease inhibitors in the induction of HSC/HPC mobilization. Bone marrow (BM) extracellular extracts that were obtained from murine femurs after 0.5 Gy of TBI contained an inhibitor of elastase. Also, after low-dose TBI, both Serpina1 mRNA and protein concentrations were increased in BM extracts, compared with extracts that were obtained from controls. The inhibitory activity in BM extracts of irradiated mice was reversed by addition of an Ab directed against Serpina1. To further study a possiblein vivorole of Serpina1 in HSC/HPC mobilization, we administered Serpina1 before IL-8 injection. This administration resulted in an almost complete inhibition of HSC/HPC mobilization, whereas heat-inactivated Serpina1 had no effect. These results indicate that low-dose TBI inhibits cytokine-induced HSC/HPC mobilization and induces Serpina1 in the BM. Because exogenous administration of Serpina1 inhibits mobilization, we propose that radiation-induced Serpina1 is responsible for the inhibition of HSC/HPC mobilization. Also, we hypothesize that cytokine-induced HSC/HPC mobilization is determined by a critical balance between serine proteases and serine protease inhibitors.
- Subjects :
- Male
ALPHA-1-PROTEINASE INHIBITOR
Proteases
INTERLEUKIN-8
Time Factors
bone marrow
BLOOD
BONE-MARROW
Blotting, Western
protease inhibitors
Biology
Pharmacology
Granulocyte
Models, Biological
RADIOPROTECTIVE CAPACITY
Mice
THIOPHILIC ADSORPTION
medicine
Cell Adhesion
Animals
adhesion molecules
RNA, Messenger
Progenitor cell
Hematopoietic Stem Cell Mobilization
Mice, Inbred BALB C
Multidisciplinary
Pancreatic Elastase
Reverse Transcriptase Polymerase Chain Reaction
Stem Cells
RAPID MOBILIZATION
Elastase
Hematopoietic stem cell
Antibodies, Monoclonal
Dose-Response Relationship, Radiation
protease
Biological Sciences
COLONY-STIMULATING FACTOR
Colony-stimulating factor
Hematopoietic Stem Cells
Molecular biology
Mice, Inbred C57BL
medicine.anatomical_structure
PROGENITOR CELLS
alpha 1-Antitrypsin
Cytokines
Bone marrow
RHESUS-MONKEYS
Subjects
Details
- Language :
- English
- ISSN :
- 10916490 and 00278424
- Volume :
- 103
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Science of the United States of America
- Accession number :
- edsair.doi.dedup.....45ed7cbd068ced644194d5f5c75cfc1a