Bacillus anthracis edema toxin impairs neutrophil actin-based motility.
Inhalation anthrax results in high-grade bacteremia and is accompanied by a delay in the rise of the peripheral polymorphonuclear neutrophil (PMN) count and a paucity of PMNs in the infected pleural fluid and mediastinum. Edema toxin (ET) is one of the major Bacillus anthracis virulence factors and consists of the adenylate cyclase edema factor (EF) and protective antigen (PA). Relatively low concentrations of ET (100 to 500 ng/ml of PA and EF) significantly impair human PMN chemokinesis, chemotaxis, and ability to polarize. These changes are accompanied by a reduction in chemoattractant-stimulated PMN actin assembly. ET also causes a significant decrease in Listeria monocytogenes intracellular actin-based motility within HeLa cells. These defects in actin assembly are accompanied by a >50-fold increase in intracellular cyclic AMP and a >4-fold increase in the phosphorylation of protein kinase A. We have previously shown that anthrax lethal toxin (LT) also impairs neutrophil actin-based motility (R. L. During, W. Li, B. Hao, J. M. Koenig, D. S. Stephens, C. P. Quinn, and F. S. Southwick, J. Infect. Dis. 192:837-845, 2005), and we now find that LT combined with ET causes an additive inhibition of PMN chemokinesis, polarization, chemotaxis, and FMLP (N-formyl-met-leu-phe)-induced actin assembly. We conclude that ET alone or combined with LT impairs PMN actin assembly, resulting in paralysis of PMN chemotaxis.
Division of Infectious Diseases, University of Florida College of Medicine, Gainesville, FL 32610, USA.
Sarah E
SE
Szarowicz
Russell L
RL
During
Wei
W
Li
Conrad P
CP
Quinn
Wei-Jen
WJ
Tang
Frederick S
FS
Southwick
D000199:Actins / Q000037:antagonists & inhibitors*; D000328:Adult; D000942:Antigens, Bacterial / Q000633:toxicity*; D001408:Bacillus anthracis / Q000276:immunology / Q000472:pathogenicity*; D001427:Bacterial Toxins / Q000633:toxicity*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D000242:Cyclic AMP / Q000032:analysis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry; D005260:Female; D006801:Humans; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000382:microbiology*; D010766:Phosphorylation; D055815:Young Adult
D000199:Actins; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases