title: Anthrax lethal toxin paralyzes neutrophil actin-based motility.
abstract: 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.
authors.affiliation: Department of Medicine/Infectious Diseases, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Russell L
authors.initials: RL
authors.lastname: During
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Binghua
authors.initials: B
authors.lastname: Hao
authors.forename: Joyce M
authors.initials: JM
authors.lastname: Koenig
authors.forename: David S
authors.initials: DS
authors.lastname: Stephens
authors.forename: Conrad P
authors.initials: CP
authors.lastname: Quinn
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Southwick
mesh_terms: D000199:Actins / Q000502:physiology; D000881:Anthrax / Q000382:microbiology; D000942:Antigens, Bacterial / Q000276:immunology / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D001408:Bacillus anthracis / Q000276:immunology* / Q000378:metabolism; D001427:Bacterial Toxins / Q000276:immunology / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D003599:Cytoskeleton / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008858:Microscopy, Phase-Contrast; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
chemical_list: D000199:Actins; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D005419:Flavonoids; D047428:Protein Kinase Inhibitors; C030325:anthrax toxin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D048369:MAP Kinase Kinase 1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one