Neurite-promoting effect of α2-macroglobulin in rat cerebral cortex is mainly associated with α2-macroglobulin receptor

It has been reported that alpha 2-macroglobulin (alpha 2 M), known as a plasma protease inhibitor, promotes neurite outgrowth of cultured neurons from rat cerebral cortex. The neurons dissociated from 17-day embryonic (E17) rat cerebral cortex were cultured in the medium containing methylamine-modified alpha 2M labeled with fluorescein isothiocyanate (MA- alpha 2 M-FITC). The modified alpha 2 M was taken up by neurons and localized mainly at the base of neurites. The fluorescence intensity of internalized MA- alpha 2 M-FITC in the cell was correlated to the degree of neurites extension. An immunocytochemical study using anti-alpha 2 M receptor (alpha 2 MR) polyclonal antibody showed that the neurons cultured for a longer period were stained weaker than those cultured for a shorter period. Many alpha 2 MRs were expressed when the neurons were likely to be extending the neurites well. From the developmental study of rat cerebrum, the expression of alpha 2 MR reached a maximum at postnatal 2 days (P2) when the neurons started to exhibit active neurite extension. These observations led us to conclude that neurite promoting effect of alpha 2 M acts through alpha 2 M-alpha 2MR binding and/or the following uptake of alpha 2 M.