FVIII production by human lung microvascular endothelial cells.
While extrahepatic factor VIII (FVIII) synthesis suffices for hemostasis, the extrahepatic production sites are not well defined. We therefore investigated the ability of the human lungs to produce FVIII. Lungs from heart-beating donors who were declined for transplantation were perfused and ventilated in an isolated reperfusion model for 2 hours. A progressive accumulation of FVIII and von Willebrand factor (VWF) was recorded in the perfusion medium in 3 of 4 experiments. By contrast, factor V, fibrinogen, and immunoglobulin G (IgG) levels remained constant during the perfusion period, indicating that the accumulation of FVIII and VWF was not due to diffusion from the intercellular medium into the vascular system. Purified human lung microvascular endothelial cells produced FVIII during at least 2 passages in vitro. Altogether, these data identify the lung endothelial cells as a FVIII production site in humans.
Center for Molecular and Vascular Biology, University of Leuven, Belgium. jacquemin@med.kuleuven.be
Marc
M
Jacquemin
Arne
A
Neyrinck
Maria Iris
MI
Hermanns
Renaud
R
Lavend'homme
Filip
F
Rega
Jean-Marie
JM
Saint-Remy
Kathelijne
K
Peerlinck
Dirk
D
Van Raemdonck
Charles James
CJ
Kirkpatrick
D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005169:Factor VIII / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000098:blood supply* / Q000378:metabolism; D008833:Microcirculation; D011652:Pulmonary Circulation; D015424:Reperfusion; D014841:von Willebrand Factor / Q000032:analysis
D014841:von Willebrand Factor; D005169:Factor VIII