Lee MJ, Park JY, Lee SY, Lee JS, Jung DK, Bae YS, Kwak JY.
Modulation of constitutive and delayed apoptosis by brefeldin A
in human neutrophils.
Int Immunopharmacol. 2003 Jun;3(6):835-43.
Medical Research Center for Cancer Molecular Therapy, Busan
602-103, South Korea.
Neutrophil apoptosis is a constitutive process that can be
enhanced or delayed by various stimuli. In this study, the
effect of brefeldin A (BFA), which affects the biological
process of secretion, on constitutive and delayed apoptosis of
neutrophils was investigated. Neutrophil apoptosis was
determined after culturing for 20 h in vitro by morphological
changes, annexin V staining, and DNA electrophoresis. BFA
dose-dependently increased the constitutive apoptotic rate of
neutrophils. The delay of apoptosis induced by
granulocyte-macrophage colony-stimulating factor (GM-CSF) and
lipopolysaccharide (LPS) was also blocked by BFA. However, this
effect of BFA was less marked when neutrophils were treated with
dexamethasone, interleukin-8 (IL-8), or dibutyryl cAMP (dbcAMP).
Moreover, the delay of neutrophil apoptosis induced by
rottlerin, a specific inhibitor of protein kinase C (PKC)-delta,
was significantly abrogated by BFA. Although BFA-induced
apoptosis was not blocked by the caspase-3 inhibitor, zDEVD-fmk,
myeloid cell leukemia-1 (Mcl-1) expression levels were
downregulated by BFA. These results suggest that derangement of
vesicular protein transport may be involved in the apoptosis of
neutrophils, and that the action of BFA on apoptosis is
dependent on changes in the expression of Mcl-1.PMID:
12781700
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