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Blood. 2016 Jul 7;128(1):104-9. doi: 10.1182/blood-2015-12-684688. Epub 2016 May 12.

Patterns of expression of factor VIII and von Willebrand factor by endothelial cell subsets in vivo.

Author information

1
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;
2
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;
3
Cyrus Tang Hematology Center, Soochow University, Suzhou, People's Republic of China;
4
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK;
5
Palo Alto Veterans Institute for Research, Palo Alto, CA;
6
Department of Cell and Gene Therapy, Biogen, Cambridge, MA; and.
7
Department of Pathology, Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY.
8
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;

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

FVIII:

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.

PMID:
27207787
PMCID:
PMC4937354
DOI:
10.1182/blood-2015-12-684688
[Indexed for MEDLINE]
Free PMC Article

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