Increased expression of chemokines (MCP-1, MIP-1alpha, RANTES) after peripheral nerve transection.

After nerve injury, recruitment of circulating macrophages into the endoneurium is essential for degeneration and subsequently for successful regeneration. However, the factors leading to macrophage recruitment are not known in detail. Chemokines are one of many possible factors influencing recruitment. In this study we wanted to examine, immunohistochemically, the expression of MCP-1, MIP-1alpha and RANTES from 6 hours up to 4 weeks after transection of rat sciatic nerve. An increased expression of MCP-1 was noted already 6 hours after transection, mainly in Schwann cells. Later, the MCP-1 positive staining was seen also in macrophages, fibroblast-like cells and endothelial cells. An increased number of MIP-1alpha positive cells could be noticed after 24 hours, the maximum expression in Schwann cells was noted at the 5-day timepoint. Later, part of the positive cells appeared to be macrophages. RANTES was mainly expressed in inflammatory cells. Endothelial cells in the epi- and endoneurium showed positive staining for every chemokine studied after transection. The contralateral non-operated nerves showed an increased number of positive cells for MCP-1 and MIP-1alpha. In the control nerves MCP-1 and MIP-1alpha positive cells were scattered throughout the endoneurium. This study shows that increased expression of chemokines takes place within endoneurium after peripheral nerve transection. Thus, it is probable that chemokines can take part in the recruitment of macrophages. It further shows that there is an increased expression of the studied chemokines in the non-operated contralateral nerves. Even in normal conditions chemokines are needed, probably to keep resident macrophages within endoneurium.