title: Patterns of expression of factor VIII and von Willebrand factor by endothelial cell subsets in vivo.
abstract: Circulating factor VIII (FVIII) is derived from liver and from extrahepatic sources probably of endothelial origin, but the vascular sites of FVIII production remain unclear. Among organs profiled, only liver and lymph nodes (LNs) show abundant expression of F8 messenger RNA (mRNA). Transcriptomic profiling of subsets of stromal cells, including endothelial cells (ECs) from mouse LNs and other tissues, showed that F8 mRNA is expressed by lymphatic ECs (LECs) but not by capillary ECs (capECs), fibroblastic reticular cells, or hematopoietic cells. Among blood ECs profiled, F8 expression was seen only in fenestrated ECs (liver sinusoidal and renal glomerular ECs) and some high endothelial venules. In contrast, von Willebrand factor mRNA was expressed in capECs but not in LECs; it was coexpressed with F8 mRNA in postcapillary high endothelial venules. Purified LECs and liver sinusoidal ECs but not capECs from LNs secrete active FVIII in culture, and human and mouse lymph contained substantial
  
  
  
  C activity. Our results revealed localized vascular expression of FVIII and von Willebrand factor and identified LECs as a major cellular source of FVIII in extrahepatic tissues.
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA; Palo Alto Veterans Institute for Research, Palo Alto, CA; Cyrus Tang Hematology Center, Soochow University, Suzhou, People's Republic of China;
authors.forename: Junliang
authors.initials: J
authors.lastname: Pan
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA; The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA;
authors.forename: Thanh Theresa
authors.initials: TT
authors.lastname: Dinh
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA; The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA;
authors.forename: Anusha
authors.initials: A
authors.lastname: Rajaraman
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA; The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA;
authors.forename: Mike
authors.initials: M
authors.lastname: Lee
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA; The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA;
authors.forename: Alexander
authors.initials: A
authors.lastname: Scholz
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA; The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA;
authors.forename: Cathrin J
authors.initials: CJ
authors.lastname: Czupalla
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA; The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA;
authors.forename: Helena
authors.initials: H
authors.lastname: Kiefel
authors.affiliation: Cyrus Tang Hematology Center, Soochow University, Suzhou, People's Republic of China;
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK;
authors.forename: Lijun
authors.initials: L
authors.lastname: Xia
authors.affiliation: Palo Alto Veterans Institute for Research, Palo Alto, CA;
authors.forename: John
authors.initials: J
authors.lastname: Morser
authors.affiliation: Department of Cell and Gene Therapy, Biogen, Cambridge, MA; and.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY.
authors.forename: Laura
authors.initials: L
authors.lastname: Santambrogio
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, CA; Palo Alto Veterans Institute for Research, Palo Alto, CA; The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA;
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Butcher
mesh_terms: D000818:Animals; D002196:Capillaries / Q000166:cytology / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005169:Factor VIII / Q000096:biosynthesis*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007678:Kidney Glomerulus / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D014699:Venules / Q000166:cytology / Q000378:metabolism; D014841:von Willebrand Factor / Q000096:biosynthesis*
chemical_list: D014841:von Willebrand Factor; C078147:F8 protein, human; D005169:Factor VIII