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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.

In the present study rat sciatic nerves (n = 60) were transected; in half of the animals nerve was allowed to regenerate freely, in the other half the regeneration was prevented by suturing beside the point of transection. Macrophages were stained with ED-1 antibody and counted (number/mm2) in both the epi- and endoneurium 3, 7, 14, 48 and 56 days post transection. Macrophages were observed first in the epineurium; the local density of macrophages was considerably higher in the epineurium than in the endoneurium during the first few days. The number of macrophages in the epineurium was maximal at 3 days (1,000-2,000/mm2), and thereafter it declined sharply. In the endoneurium macrophages were most abundant after 2 weeks (1,000/mm2), after which their number declined steadily. A migration of epineurial macrophages appeared to take place through the perineurium from epineurial areas containing a high concentration of macrophages. Initially an endoneurial accumulation of macrophages was noted in the subperineurial area. These findings suggest an alternative route for macrophages into the endoneurial space. No statistical difference was observed between the regenerating and non-regenerating experimental groups. The present study indicates that regenerating axons do not have an effect on the number of macrophages in either the epineurium or the endoneurium.

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