Sublethal Doses of Anthrax Lethal Toxin on the Suppression of Macrophage Phagocytosis

Kau, Jyh-Hwa; Sun, Der-Shan; Huang, Hsuan-Shun; Lien, Te-Sheng; Huang, Hsin-Hsien; Lin, Herng Ching; Chang, Hsin-Hou

doi:10.1371/journal.pone.0014289

Cited by 21 publications

(35 citation statements)

References 52 publications

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“…This hypothesis remains unconfirmed; however, the findings from one of our previous studies might support this hypothesis. 52 LT treatments can greatly enhance the mortality of mice with sublethal Escherichia coli. 52 The suppression of macrophage is likely involved, and constructing a reduced coagulation system remains feasible.…”

Section: Discussionmentioning

confidence: 99%

“…52 LT treatments can greatly enhance the mortality of mice with sublethal Escherichia coli. 52 The suppression of macrophage is likely involved, and constructing a reduced coagulation system remains feasible. 52 We suggest a novel strategy for coagulation intervention to treat anthrax.…”

Section: Discussionmentioning

confidence: 99%

“…52 The suppression of macrophage is likely involved, and constructing a reduced coagulation system remains feasible. 52 We suggest a novel strategy for coagulation intervention to treat anthrax. Approved by the US Food and Drug Administration, rFVIII is a drug used for genetic and acquired FVIII deficiencies.…”

Section: Discussionmentioning

confidence: 99%

“…4,5,14,16,52,55,56 For cell and animal studies, high-performance liquid chromatography (HPLC)-purified LF and PA were reconstituted as LT in a ratio of 1:5, which resembles the ratio of PA and LF in the culture supernatants of B. anthracis. The LPS contamination was monitored using a Limulus Amoebocyte Lysate QCL -1000 kit (Lonza, Walkersville, MD, USA).…”

Section: Methodsmentioning

confidence: 99%

“…52 Human hepatoma cell lines HepG2 (ATCC HB8055) and Huh-7 were maintained in a Dulbecco's modified Eagle's medium containing 10% fetal bovine serum. After the cells were changed to a serumfree medium, the cells (2 £ 10 4 /well) were treated with various concentrations (0.2, 2, or 4 mg/mL) of LT (LF:PA D 1:5) in a 96-well cell culture dish.…”

Section: Cell Viability Analysismentioning

confidence: 99%

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Acquired coagulant factor VIII deficiency induced byBacillus anthracislethal toxin in mice

Sun¹,

Lee

Kau

et al. 2015

Virulence

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(2015) Acquired coagulant factor VIII deficiency induced by Bacillus anthracis lethal toxin in mice, Virulence, 6:5, 466-475, DOI: 10.1080/21505594.2015 Keywords: Anthrax, coagulation factor VIII, hemorrhage, lethal toxinMice treated with anthrax lethal toxin (LT) exhibit hemorrhage caused by unknown mechanisms. Moreover, LT treatment in mice induced liver damage. In this study, we hypothesized that a suppressed coagulation function may be associated with liver damage, because the liver is the major producing source of coagulation factors. The hepatic expression of coagulant factors and the survival rates were analyzed after cultured cells or mice were exposed to LT. In agreement with our hypothesis, LT induces cytotoxicity against hepatic cells in vitro. In addition, suppressed expression of coagulation factor VIII (FVIII) in the liver is associated with a prolonged plasma clotting time in LT-treated mice, suggesting a suppressive role of LT in coagulation. Accordingly, we further hypothesized that a loss-of-function approach involving treatments of an anticoagulant should exacerbate LT-induced abnormalities, whereas a gain-offunction approach involving injections of recombinant FVIII to complement the coagulation deficiency should ameliorate the pathogenesis. As expected, a sublethal dose of LT caused mortality in the mice that were non-lethally pretreated with an anticoagulant (warfarin). By contrast, treatments of recombinant FVIII reduced the mortality from a lethal dose of LT in mice. Our results indicated that LT-induced deficiency of FVIII is involved in LT-mediated pathogenesis. Using recombinant FVIII to correct the coagulant defect may enable developing a new strategy to treat anthrax.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Cell Viability Analysismentioning

confidence: 99%

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Acquired coagulant factor VIII deficiency induced byBacillus anthracislethal toxin in mice

Sun¹,

Lee

Kau

et al. 2015

Virulence

Self Cite

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Anthrax Infection

Remy¹,

Hicks²,

Eichacker³

2015

Human Emerging and Re‐emerging Infections

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Platelets in Inflammation and Immune Modulations: Functions Beyond Hemostasis

Huang

Chang

2012

Arch. Immunol. Ther. Exp.

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Platelets play central roles for maintaining the homeostasis of the blood coagulation. As they are also involved in immune responses and host defenses, increasing evidences have suggested that platelets exert other roles beyond their well-recognized function in preventing bleeding. This review is focused on inflammation, allergy and immune modulations of platelets. Platelets conduct immunoregulation through secretion of functional mediators, interaction with various immune cells, endothelial cells and beneficial for the leukocyte infiltration to inflamed/allergic tissues. In these regulations, the leukocytes are influenced by and receiving the signals from platelets. In contrast, rare attentions were focused on platelet regulations by immune system. An intriguingly example in the intravenous immunoglobulin (IVIg) treatment is discussed, in which dendritic cells exert anti-inflammatory effect through platelets. This further suggests that coagulant and immune systems are tightly associated rather than separate entities. The cross-talks between these two systems implicate that platelet therapy may have application beyond thrombosis, and immune interventions may have potentials to treat thrombosis diseases.

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Sublethal Doses of Anthrax Lethal Toxin on the Suppression of Macrophage Phagocytosis

Cited by 21 publications

References 52 publications

Acquired coagulant factor VIII deficiency induced byBacillus anthracislethal toxin in mice

Acquired coagulant factor VIII deficiency induced byBacillus anthracislethal toxin in mice

Anthrax Infection

Platelets in Inflammation and Immune Modulations: Functions Beyond Hemostasis

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