Increased expression of glomerular von Willebrand factor after irradiationof the mouse kidney

Ionizing irradiation has been shown to induce an increased release of von W illebrand factor (vWF) in human endothelial cells in vitro. The present stu dy was undertaken to investigate whether an increase in expression of vWF a lso occurs in glomerular endothelial cells in vivo after irradiation of the kidney. Increased expression of VWF may initiate prothrombotic changes, an d the resultant vascular damage could cause renal failure. The amount of ad herent leukocytes in the renal cortex after irradiation was also quantified , since this may contribute to the histological changes that occur after ir radiation. Changes in expression of glomerular VWF and in the amount of leu kocytes were related to the development of impairment of renal function, as assessed with the [Cr-51]EDTA retention assay. Mice were given bilateral i rradiation (single dose of 16 Gy) or were sham-irradiated and were sacrific ed at intervals of 1 day to 40 weeks after irradiation. Immunohistochemical analysis of kidney cryosections was performed using a polyclonal vWF antib ody or monoclonal CD45 antibody (leukocyte common antigen). The amount of g lomerular VWF staining and CD45 staining in the renal cortex (percentage su rface coverage) was quantified using a computerized image analyzer. The mea n glomerular VWF staining in the nonirradiated kidneys was 34.4 +/- 6.2% (m ean +/- SEM, 10 weeks after sham treatment). After irradiation, the express ion of glomerular vWF increased gradually from 10 weeks to 53.4 +/- 3.6% at 40 weeks. The total number of leukocytes in the renal cortex of nonirradia ted mice at 10 weeks after sham treatment was low, with a mean area of 1.0 +/- 0.09%, whereas in the irradiated kidneys the relative tissue area cover ed by leukocytes increased to 7.6 +/- 2.1% at 40 weeks. These alterations p receded impairment of renal function. The extent to which these changes are causally related to impairment of function will be the subject of future s tudy using specific antithrombotic and anti-inflammatory agents, (C) 1998 b y Radiation Research Society.