TY - JOUR
T1 - Patterns of expression of factor VIII and von Willebrand factor by endothelial cell subsets in vivo
AU - Pan, Junliang
AU - Dinh, Thanh Theresa
AU - Rajaraman, Anusha
AU - Lee, Mike
AU - Scholz, Alexander
AU - Czupalla, Cathrin J.
AU - Kiefel, Helena
AU - Zhu, Li
AU - Xia, Lijun
AU - Morser, John
AU - Jiang, Haiyan
AU - Santambrogio, Laura
AU - Butcher, Eugene C.
N1 - Publisher Copyright:
© 2016, American Society of Hematology. All rights reserved.
PY - 2016/7/7
Y1 - 2016/7/7
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2015-12-684688
DO - 10.1182/blood-2015-12-684688
M3 - Article
C2 - 27207787
AN - SCOPUS:85019487003
SN - 0006-4971
VL - 128
SP - 104
EP - 109
JO - Blood
JF - Blood
IS - 1
ER -