In vitro and in vivo expression of endothelial von Willebrand factor and leukocyte accumulation after fractionated irradiation

Previous investigations have demonstrated an increased release of von Wille brand factor (VWF; also known as VWF) in endothelial cells after high singl e-dose irradiation in vitro. We have also found increased levels of Vwf pro tein in mouse glomeruli after a high single dose of renal irradiation in vi vo. In addition, increased numbers of leukocytes were observed in the renal cortex after irradiation in vivo. The aim of the present study was to inve stigate and quantify these biological processes after clinically relevant f ractionated irradiation and to relate them to changes in renal function. A significantly greater increase in release of VWF was observed in cultured h uman umbilical vein endothelial cells (HUVECs) after fractionated irradiati on (20 x 1.0 Gy) than after a single dose of 20 Gy (147% compared to 115% o f control, respectively, P < 0.0005). In contrast with the in vitro observa tions, glomerular Vwf staining was lower after fractionated irradiation in vivo (20 x 2.0 Gy or 10 x 1.6 Gy +/- re-irradiation) than after a single do se of 16 Gy. The number of leukocytes accumulating in the renal cortex was also lower after fractionated in vivo irradiation than after a single radia tion dose. The onset of these events preceded renal functional and histopat hological changes by approximately 10 weeks. These data indicate that radia tion-induced changes in endothelial. VWF expression after in vivo irradiati on may be distinct from the in vitro observations. Increased VWF expression may reflect pivotal processes in the pathogenesis of late radiation nephro pathy and provide a clue to appropriate timing of pharmacological intervent ion. (C) 2000 by Radiation Research Society.