| 622 |
Anthrax
Lethal Toxin Paralyzes Neutrophil
Actin-Based Motility |
Russell
L. During, Wei Li, Binghua Hao, Joyce M. Koenig, David S. Stephens, Conrad P. Quinn, Frederick
S. Southwick |
Bacillus
anthracis, paralysis, innate immune system, anthrax lethal toxin (LT), neutrophil chemotaxis,Polymorphonuclear
neutrophils (PMNs), apoptosis, necrosis, chemokinesis |
Untreated and LT-treated PMNs
(1105 cells in 2 mL of RPMI) were added to 35-mm glass-bottom microwell dishes (MatTek Cultureware)
coated with 0.1% fibronectin (Sigma).
|
inverted
microscopy, video microscopy |
human |
|
PMNs |
| |
Bacillus anthracis causes high-level bacteremia, strongly
suggesting paralysis of the innate immune system. We have examined the effects of anthrax lethal
toxin (LT) on human neutrophil chemotaxis, a process that requires actin filament assembly.
Polymorphonuclear neutrophils (PMNs) treated with a sublethal concentration of LT (50 ng/mL)
for 2 h demonstrated insignificant apoptosis or necrosis. However, this same concentration slowed
human PMN formylmethionylleucylphenylalanine (FMLP)–stimulated chemokinesis by 160%, markedly
reduced polar morphology, and rendered PMNs incapable of responding to a chemotactic gradient.
These changes were accompanied by a 150% reduction in FMLP-induced actin filament assembly.
One hour of exposure to LT failed to impair polarity or actin assembly, and the effects of LT
were independent of mitogen-activated protein kinase kinase 1 inhibition. We conclude that 2
h of exposure to LT markedly impairs PMN actin assembly, and reductions in actin filament content
are accompanied by a profound paralysis of PMN chemotaxis. |
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