Investigation of the Expression of Fractalkine and the Infiltration Characteristics of Fractalkine Receptor Positive Cells and Macrophages in Cisplatin-induced Acute Renal Failure in Mice

Kim, Tae Young; Jin, Nam Woo; Kim, Sun Min; Lee, Kyung Eun; Ahn, Jihyun; Kim, Su Hyun; Oh, Dong Jin; Yu, Suk Hee

Abstract

PURPOSE: The aim of the present study was to investigate the expression and the infiltration characteristics of fractalkine (CX3CL1)/ its receptor (CX3CR1) positive cells and macrophages in cisplatininduced ARF (CisARF).
METHODS
Cisplatin (30 mg/kg) was injected intraperitoneally into wild-type C57BL/6 mice. Time course of CX3CL1 expression/CX3CR1 positive cells and macrophage infiltration in CisARF was investigated by using immunofluorescence for CX3CL1, CX3CR1 and CD 11b in the outer medullary region. And we performed a study whether there was a significant difference of macrophages infiltration between wild type and caspase-1- deficient mice, which was protective against CisARF.
RESULTS
(1) Renal dysfunction was the most severe on day 3. (2) The intensity of immunofluorecence staining for CX3CL1 showed that there was a significantly increased expression in the tubulointerstitium rather than blood vessels in cisplatin-treated mice. There were no differences in CX3CR1 positive cells between vehicle and cisplatin-treated mice. (3) Macrophages infiltration was augmented from day 2 after cisplatin administration and preceded the development of CisARF. Macrophages infiltration in caspase-1 -/- mice was significantly lower than wild- type mice in CisARF.
CONCLUSION
Our data demonstrated that CX3CL1 expression and macrophage infiltration in CisARF precedes the development of ARF, especially in the tubulointerstitium rather than blood vessels. However, recent reports showed that the blockade of CX3CR1 positive cells and depletion of macrophages could not be protective against CisARF. Therefore, further study is required to determine the role of other inflammatory cells such as natural killer cells in CisARF.