title: Hexa-acylated LPS-lipid A deploys the appropriate level of fibrin to confer protection through MyD88.
abstract: OBJECTIVE
  Fibrin has been demonstrated to function protectively against pathogens in our previous studies, but we observed that a very high level of fibrin played a negative role during infection. We performed this research to address the complication.
  
  
  METHODS
  After infection, mice were monitored daily and harvested on day 4. The fibrin levels within the tissue samples were quantified by Western-blot. The in situ assay was used to detect plasminogen activators, protein C-ase and prothrombinase activation. PT-PCR was used to test coagulation factors expression.
  
  
  RESULTS
  Mice treated with Coumadin showed that the protection correlates with fibrin levels. By interacting with Toll-like receptor 4, the hexa-acylated lipopolysaccharide, although not the tetra-acylated lipopolysaccharide, activates coagulation and regulates plasminogen activator inhibitor 1, thrombin activatable fibrinolysis inhibitor and thrombomodulin expression through myeloid differentiation factor 88, leading to plasminogen activators, protein C-ase and prothrombinase activation and fibrin formation. Because of the regulation, fibrin formation was controlled to deposit appropriate levels and confer protection.
  
  
  CONCLUSIONS
  We demonstrated that the appropriate level of fibrin formation was deployed by hexa-acylated LPS-lipid A through myeloid differentiation factor 88 to confer protection.
authors.affiliation: Yuhuangding Hospital, 20 Yuhuangding East Road, Zhifu District, Yantai, China 264000.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Immunology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dongda Street, Fengtai District, Beijing, China, 100071.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Yuhuangding Hospital, 20 Yuhuangding East Road, Zhifu District, Yantai, China 264000.
authors.forename: Dongxia
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Immunology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dongda Street, Fengtai District, Beijing, China, 100071.
authors.forename: Liangyan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Immunology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dongda Street, Fengtai District, Beijing, China, 100071. Electronic address: ldy612@126.com.
authors.forename: Deyan
authors.initials: D
authors.lastname: Luo
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D005337:Fibrin / Q000378:metabolism*; D008050:Lipid A / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000502:physiology*; D010930:Plague / Q000097:blood / Q000378:metabolism / Q000517:prevention & control*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism; D011486:Protein C / Q000378:metabolism; D018180:Thrombomodulin / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D008050:Lipid A; D053594:Myeloid Differentiation Factor 88; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D018180:Thrombomodulin; D051197:Toll-Like Receptor 4; D005337:Fibrin; D010960:Plasminogen Activators
keywords: Lipopolysaccharide; Yersinia pestis; coagulation; fibrin