Effect of gamma-radiation on healthy rat liver and gene expression of chemokines: In vivo and in vitro studies.

Abstract

e21107 Background: Primary liver tumors or liver metastasis are treated by gamma-irradiation. However, the liver is considered to be a radio-sensitive organ. Methods: Rats were exposed to single-dose gamma-irradiation (25-Gy) with the liver being on focus. Results: Single dose gamma-irradiation induces only a mild liver damage probably due to transient accumulation of granulocytes (not macrophages) into the liver. Immunohistologically, 3-6 hours after irradiation an increased number of neutrophil granulocytes (but not of mononuclear phagocytes) was observed attached to portal vessels between and around the portal (myo) fibroblasts (SMA and Thy-1+ cells). MCP-1/CCL2 staining was also detected in the portal vessel walls including some cells of the portal area. A significant induction of CC-(MCP-1/CCL2, MCP-3/CCL7) and CXC-chemokines (KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5) gene expression was observed in total-RNA from irradiated livers. In laser capture micro-dissected samples, an early (1-3h) up-regulation of CCL2, CXCL1, CXCL8 and CXCR2-gene expression was detected in the portal area; with exception of CXCL1-gene expression, up-regulated in the parenchyma. Administration of an antibody against MCP-1/CCL2 before irradiation led to increase in gene expression of IFN-gamma and IP- 10/CXCL10 in liver tissue without influencing the recruitment of granulocytes. The CCL2, CXCL1, CXCL2 and CXCL5 genes were strongly expressed and further up-regulated in (myo) fibroblasts (LMFs) after irradiation (8Gy) when compared to liver macrophages or hepatocytes. Conclusions: Gamma-irradiation of the liver induces a transient accumulation of granulocytes within the portal area. (Myo) fibroblasts of the portal vessels may be one of the major sources of the chemokines involved in neutrophil recruitment. Inhibition of more than one chemokines (e.g., CXCL1 and CXCL8) may be necessary to reduce leukocytes recruitment. No significant financial relationships to disclose.