title: Non-hematopoietic EPCR regulates the coagulation and inflammatory responses during endotoxemia.
abstract: BACKGROUND
  Activated protein C (APC) protects the host from severe sepsis. Endothelial protein C receptor (EPCR) is expressed on both hematopoietic leukocytes and non-hematopoietic endothelium, and plays a key role in protein C activation.
  
  
  OBJECTIVE
  We explore the influence of EPCR deletion on the responses to lipopolysaccharide (LPS) and then determine whether the observed differences are due to loss of hematopoietic or non-hematopoietic EPCR.
  
  
  RESULTS
  After LPS challenge, EPCR null (Procr(-/-)) mice exhibited more thrombin and cytokine generation, neutrophil sequestration in the lung and a higher mortality rate than Procr(+/-) mice. Procr(+/-) BM/Procr(-/-) (non-hematopoietic Procr(-/-)) and Procr(-/-) BM/Procr(+/-) (hematopoietic Procr(-/-)) chimeric mice were generated by bone marrow (BM) transplantation. Compared with control Procr(+/-) mice, non-hematopoietic Procr(-/-) mice exhibited reduced protein C activation by thrombin and exaggerated responses to LPS challenge, whereas Procr(+/-) mice and hematopoietic Procr(-/-) mice exhibited similar protein C activation by thrombin and similar responses to LPS challenge.
  
  
  CONCLUSIONS
  EPCR deletion exaggerates the host responses to LPS primarily due to deficiency of EPCR on the non-hematopoietic cells.
authors: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors: X
authors: X
authors: Zheng
authors: W
authors: W
authors: Li
authors: Y
authors: Y
authors: Song
authors: Y
authors: Y
authors: Hu
authors: G L
authors: GL
authors: Ferrell
authors: N L
authors: NL
authors: Esmon
authors: C T
authors: CT
authors: Esmon
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D016207:Cytokines / Q000096:biosynthesis; D000074283:Endothelial Protein C Receptor; D004730:Endothelium, Vascular / Q000378:metabolism; D019446:Endotoxemia / Q000097:blood* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011486:Protein C / Q000378:metabolism*; D011956:Receptors, Cell Surface; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology
chemical_list: D016207:Cytokines; D000074283:Endothelial Protein C Receptor; D006023:Glycoproteins; D008070:Lipopolysaccharides; C080248:Procr protein, mouse; D011486:Protein C; D011956:Receptors, Cell Surface; D013917:Thrombin