Anthrax Lethal Toxin Paralyzes Neutrophil Actin-Based Motility

• Published in: The Journal of infectious diseases Vol. 192; no. 5; pp. 837 - 845
• Main Authors: During, Russell L., Li, Wei, Hao, Binghua, Koenig, Joyce M., Stephens, David S., Quinn, Conrad P., Southwick, Frederick S.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.09.2005; University of Chicago Press; Oxford University Press
• Subjects: Actins; Actins - physiology; Anthrax; Anthrax - microbiology; Antigens, Bacterial - immunology; Antigens, Bacterial - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis - immunology; Bacillus anthracis - immunology; Bacillus anthracis - metabolism; Bacteria; Bacterial Toxins - immunology; Bacterial Toxins - pharmacology; Biological and medical sciences; Blood; Chemotaxis; Chemotaxis - drug effects; Cytoskeleton - physiology; Flavonoids - pharmacology; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Humans; Infectious diseases; Macrophages; MAP Kinase Kinase 1 - antagonists & inhibitors; MAP Kinase Kinase 1 - metabolism; Medical sciences; Microbiology; Microfilaments; Microscopy, Phase-Contrast; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; Necrosis; Neutrophils; Neutrophils - drug effects; Neutrophils - immunology; Neutrophils - microbiology; Protein Kinase Inhibitors - pharmacology; Toxins; Infection; Bacillus anthracis; Toxin; Motility; Bacillales; Microbiology; Actin; Anthrax; Bacteriosis; Bacteria; Neutrophil; Bacillaceae
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/432516

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 >60%, markedly reduced polar morphology, and rendered PMNs incapable of responding to a chemotactic gradient. These changes were accompanied by a >50% 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