| Autor: |
Lenarczyk M; Radiation Biosciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Alsheikh AJ; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Cohen EP; Department of Medicine, Division of Nephrology, New York University, New York, NY 10016, USA., Schaue D; Department of Radiation Oncology, University of California at Los Angeles, Los Angeles, CA 90095, USA., Kronenberg A; Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA., Geurts A; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Klawikowski S; Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA., Mattson D; Department of Physiology, Medical College of Georgia, Augusta, GA 30912, USA., Baker JE; Radiation Biosciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA. |
| Abstrakt: |
Heart disease is a significant adverse event caused by radiotherapy for some cancers. Identifying the origins of radiogenic heart disease will allow therapies to be developed. Previous studies showed non-targeted effects manifest as fibrosis in the non-irradiated heart after 120 days following targeted X-irradiation of the kidneys with 10 Gy in WAG/RijCmcr rats. To demonstrate the involvement of T cells in driving pathophysiological responses in the out-of-field heart, and to characterize the timing of immune cell engagement, we created and validated a T cell knock downrat on the WAG genetic backgrou nd. Irradiation of the kidneys with 10 Gy of X-rays in wild-type rats resulted in infiltration of T cells, natural killer cells, and macrophages after 120 days, and none of these after 40 days, suggesting immune cell engagement is a late response. The radiation nephropathy and cardiac fibrosis that resulted in these animals after 120 days was significantly decreased in irradiated T cell depleted rats. We conclude that T cells function as an effector cell in communicating signals from the irradiated kidneys which cause pathologic remodeling of non-targeted heart. |
