Expression of chemokines and their receptors in nephrotoxic serum nephritis

Background. Chemokines play a major role in leukocyte infiltration in infla mmatory kidney diseases. The specificity of the chemokine action is determi ned by the restricted expression of the corresponding receptors on leukocyt es. We therefore simultaneously studied the expression of CC-chemokine and CC-chemokine receptor 1-5 (CCR 1-5) mRNA in an accelerated model of nephrot oxic nephritis in CD-1 mice. Methods. Kidneys were harvested at day 0, 2 and 7. Induction of nephritis w as confirmed by assessment of albuminuria by ELISA and by histological eval uation. RNA was prepared from cortex and isolated glomeruli. RNase protecti on assays were performed to study the expression of chemokines, RNase prote ction assays as well as quantitative RT-PCR assays to study the expression of chemokine receptors. Results. in the cortex of nephritic kidneys mRNA for MCP-1 was increased 5- fold on day 2 and increased 4-fold on day 7 as compared to controls. mRNA f or RANTES was increased 5-fold on day 7 and mRNA for IP-10 6-fold on day 7. The increase of mRNA for the chemokine receptors CCR1 and 5 was between 2- fold and 3-fold determined by RNase protection assay and for CCR1, 2 and 5 between 2- and 4-fold as determined by RT-PCR. In isolated glomeruli we fou nd by RT-PCR an increase of CCR1, CCR2 and CCR5 of between 3 and 12-fold. Conclusion. These results show that chemokines and their specific chemokine receptors are increased in parallel in this model of glomerulonephritis, c onsistent with the potential role of the chemokine system in leukocyte recr uitment to the immune injured kidney.