title: Platelets, inflammatory cells, von Willebrand factor, syndecan-1, fibrin, fibronectin, and bacteria co-localize in the liver thrombi of Bacillus anthracis-infected mice.
abstract: Vascular dysfunction and thrombosis have been described in association with anthrax infection in humans and animals but the mechanisms of these dysfunctions, as well as the components involved in thrombi formation are poorly understood. Immunofluorescent microscopy was used to define the composition of thrombi in the liver of mice challenged with the Bacillus anthracis Sterne spores. Lethal infection with the toxigenic Sterne strain, in contrast to the non-lethal, non-toxigenic delta-Sterne strain, demonstrated time-dependent increase in the number of vegetative bacteria inside the liver sinusoids and central vein. Massive appearance of thrombi typically occluding the lumen of the vessels coincided with the sudden death of infected animals. Bacterial chains in the thrombi were stained positive for syndecan-1 (SDC-1), fibronectin, and were surrounded by fibrin polymers, GPIIb-positive platelets, von Willebrand Factor (vWF), CD45-positive leukocytes, and massive amount of shed SDC-1. Experiments with human umbilical vein endothelial cells (HUVECs) demonstrated the active role of the host response to the secreted pathogenic factors of bacteria during the onset of the pro-thrombotic condition. The bacterial culture supernatants, as well as the isolated proteins (the pore-forming toxin anthrolysin O and phospholipase C) induced release of vWF, while anthrolysin O, sphingomyelinase and edema toxin induced release of thrombin from HUVECs and polymerization of fibrin in the presence of human plasma.
  
  
  CONCLUSIONS
  Our findings suggest that activation of endothelium in response to infection can contribute to the formation of occlusive thrombi consisting of aggregated bacteria, vWF, shed SDC-1, fibrin, activated platelets, fibronectin and leukocytes.
authors: National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USA. spopov@gmu.edu
authors: Taissia G
authors: TG
authors: Popova
authors: Bryan
authors: B
authors: Millis
authors: Charles
authors: C
authors: Bailey
authors: Serguei G
authors: SG
authors: Popov
mesh_terms: D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D001408:Bacillus anthracis / Q000235:genetics / Q000502:physiology*; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D008099:Liver / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D053668:Syndecan-1 / Q000378:metabolism*; D013927:Thrombosis / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D005353:Fibronectins; D053668:Syndecan-1; D014841:von Willebrand Factor; D005337:Fibrin