Studies of Schwann cell proliferation. II. Characterization of the stimulation and specificity of the response to a neurite membrane fraction

When prepared by methods utilized in our laboratory, pure populations of Schwann cells in culture do not divide, but, after recombination with peripheral sensory neurons or their processes, proliferate rapidly (Wood and Bunge, 1975, Nature (Lond.) 256:661--664). In this paper, we demonstrate that a membrane fraction prepared from sensory ganglion neurites is also mitogenic for Schwann cells and increases the labeling index (assessed by autoradiography after incubation of cells with tritiated thymidine) from less than 0.2 to 10% for primary cells, and from 0.4 to 18--19% for replated cells. The increased responsiveness of replated cells may reflect their greater access to the neurite membranes which is a consequence of the elimination of multiple cell layers after replating and the removal of the basal lamina. This stimulation was specific; addition of membrane preparations from other cell types (3T3, C1300, etc.) was not mitogenic. Ultrastructural analysis demonstrated apparent binding of neurite membranes to Schwann cells as well as significant phagocytosis of the membranes by the cells. The uptake of nonmitogenic membranes suggests that phagocytosis per se is not the stimulus of proliferation.