Granulocyte colony-stimulating factor delays neutrophil apoptosis by inhibition of calpains upstream of caspase-3.
In: Blood, Jg. 112 (2008-09-01), Heft 5, S. 2046-54
Online
academicJournal
Zugriff:
Neutrophils have a very short life span and undergo apoptosis within 24 hours after leaving the bone marrow. Granulocyte colony-stimulating factor (G-CSF) is essential for the recruitment of fresh neutrophils from the bone marrow but also delays apoptosis of mature neutrophils. To determine the mechanism by which G-CSF inhibits neutrophil apoptosis, the kinetics of neutrophil apoptosis during 24 hours in the absence or presence of G-CSF were analyzed in vitro. G-CSF delayed neutrophil apoptosis for approximately 12 hours and inhibited caspase-9 and -3 activation, but had virtually no effect on caspase-8 and little effect on the release of proapoptotic proteins from the mitochondria. However, G-CSF strongly inhibited the activation of calcium-dependent cysteine proteases calpains, upstream of caspase-3, via apparent control of Ca(2+)-influx. Calpain inhibition resulted in the stabilization of the X-linked inhibitor of apoptosis (XIAP) and hence inhibited caspase-9 and -3 in human neutrophils. Thus, neutrophil apoptosis is controlled by G-CSF after initial activation of caspase-8 and mitochondrial permeabilization by the control of postmitochondrial calpain activity.
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Granulocyte colony-stimulating factor delays neutrophil apoptosis by inhibition of calpains upstream of caspase-3.
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Autor/in / Beteiligte Person: | van Raam BJ ; Drewniak, A ; Groenewold, V ; van den Berg TK ; Kuijpers, TW |
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Zeitschrift: | Blood, Jg. 112 (2008-09-01), Heft 5, S. 2046-54 |
Veröffentlichung: | 2021- : [New York] : Elsevier ; <i>Original Publication</i>: New York, Grune & Stratton [etc.], 2008 |
Medientyp: | academicJournal |
ISSN: | 1528-0020 (electronic) |
DOI: | 10.1182/blood-2008-04-149575 |
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