Effect of Liposome-Mediated Macrophage Depletion on Schwann Cell Proliferation During Wallerian Degeneration

The axolemma is considered a well-established mitogen, responsible for Schwann cell proliferation during Wallerian degeneration in the peripheral nerve. However, very little is known about the role of macrophages in Schwann cell proliferation. To test the possible influence of macrophages on Schwann cell proliferation during Wallerian degeneration, macrophages were depleted by dichloromethylene diphosphonate (CI2MDP)-containing liposomes in two-month old C57BL/6J mice. CI2MDP-containing liposomes were injected into the mice intravenously prior to inducing Wallerian degeneration. The injection was repeated every other day to maintain macrophage depletion. Physiologic saline was injected into the control mice. To assess macrophage depletion in vitro, cells were isolated from sciatic nerves at 1, 2, 3, 5, and 7 days post-transection (DPT) and Mac-1 positive cells attached to coverslips were counted. In an in vivo study, Mac-1 positive cells were counted on sciatic nerve sections at the same time points. Throughout the course, the number of Mac-1 positive cells in macrophage-depleted mice was less than that in the control mice both in vivo and in vitro. Schwann cell proliferation was assessed by an in vitro system that reflects in vivo status at the time of cell isolation. Schwann cells were isolated from sciatic nerves at the same time points and proliferation rate was measured by thymidine autoradiography. The proliferation rate was mildly suppressed in macrophage-depleted mice, especially for the initial 3 DPT; however, the pattern of proliferation was not significantly different from controls. These results suggest that macrophages contribute to Schwann cell proliferation during Wallerian degeneration however, their contribution may be relatively limited.