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 - Funding Information:
The authors thank Lawrence Leung and Qingyu Wu for their support. This work was supported by National Institutes of Health (NIH) grant nos. R37 AI047822, AI093981, and U19 AI090019 from the National Institute of Allergy and Infectious Diseases, grant no. R01 GM37734 from the National Institute of General Medical Sciences, an award from the Department of Veterans Affairs (E.C.B.), a seed grant from the Stanford Cardiovascular Institute (E.C.B. and J.P.), a Biogen research grant (J.P. and E.C.B.), an Immunity, Transplantation and Infection Young Investigator Award (C.J.C.), a Fellowship Award from the Ludwig Edinger Foundation (C.J.C), fellowship awards from the Crohn's and Colitis Foundation (M.L.) and from the American Heart Association (H.K.), and a Stanford Cardiovascular Institute award (T.T.D.). T.T.D. was the recipient of a fellowship under NIH training grant nos. T32 AI07290 from the NIAID and T32 HL098049 from the National Heart, Lung, and Blood Institute. A.R. was supported in part by an internship under California Institute for Regenerative Medicine grant no. TB1-01195. L.Z. was supported by a Novo Nordisk Haemophilia Research Fund in China.
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 -