Ionizing radiation enhances platelet adhesion to the extracellular matrix of human endothelial cells by an increase in the release of von Willebrand factor.
The effect of radiation on the secretion of von Willebrand factor by endothelial cells was studied in a three-compartment culture system. The release of von Willebrand factor was significantly increased at 48 h after a single gamma-radiation dose of 20 Gy in both the luminal and abluminal direction by 23 (P < 0.05) and 41% (P < 0.02), respectively. To establish whether the enhanced production of von Willebrand factor affected the thrombogenicity of the extracellular matrix, platelet adhesion to the matrix produced by a monolayer of cultured endothelial cells during 48 h after irradiation was analyzed in a perfusion chamber at high shear rate (1300 s-1). Platelet adhesion was significantly increased by irradiation both in the presence and in the absence of plasmatic von Willebrand factor by 65 (P < 0.05) and 34.5% (P < 0.005), respectively. Incubation of the perfusate with a monoclonal antibody that blocks the binding of von Willebrand factor to platelet GPIb (CLB-RAg 35) resulted in an almost complete inhibition of platelet adhesion. These data indicate that radiation enhances platelet adhesion to the the extracellular matrix by an increase in the release of von Willebrand factor by endothelial cells. This event may be important in early radiation-induced vascular pathology.
Verheij
M
M
Department of Radiotherapy, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Huis, Amsterdam.
Dewit
L G
LG
Boomgaard
M N
MN
Brinkman
H J
HJ
van Mourik
J A
JA
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D010973:Platelet Adhesiveness / Q000528:radiation effects*; D014841:von Willebrand Factor / Q000378:metabolism*
D014841:von Willebrand Factor