Dissociation of neurite-promoting activity and protease-inhibiting function of alpha 2-macroglobulin in culture.

The relationship between the neurite-promoting effect and the protease-inhibiting function of alpha 2-macroglobulin (alpha 2M) was examined in a culture of dissociated neurons from embryonic rat neocortical tissue. The neurite-promoting effect of various protease inhibitors (soybean trypsin inhibitor, alpha 1-antitrypsin, aprotinin, phenylmethanesulfonyl fluoride, leupeptin, antipain, human alpha 2M and purified rat alpha 2M) was investigated. At lower concentrations, only alpha 2M significantly promoted neurite outgrowth. Furthermore, alpha 2M-trypsin complexes, which had lost their protease-inhibiting function and exposed their receptor-recognition site, promoted neurite outgrowth more efficiently than native alpha 2M. These results indicate the possibility that the neurite-promoting effect of alpha 2M is mediated by its receptor-binding activity but is not directly related to its protease-inhibiting function.