NEURITE-PROMOTING EFFECT OF ALPHA(2)-MACROGLOBULIN IN RAT CEREBRAL-CORTEX IS MAINLY ASSOCIATED WITH ALPHA(2)-MACROGLOBULIN RECEPTOR

It has been reported that alpha(2)-macroglobulin (alpha(2)M), known as a plasma protease inhibitor, promotes neurite outgrowth of cultured n eurons from rat cerebral cortex. The neurons dissociated from 17-day e mbryonic (E17) rat cerebral cortex were cultured in the medium contain ing methylamine-modified alpha(2)M labeled with fluorescein isothiocya nate (MA-alpha(2)M-FITC). The modified alpha(2)M was taken up by neuro ns and localized mainly at the base of neurites. The fluorescence inte nsity of internalized MA-alpha(2)M-FITC in the cell was correlated to the degree of neurites extension. An immunocytochemical study using an ti-alpha(2)M receptor (alpha(2)MR) polyclonal antibody showed that the neurons cultured for a longer period were stained weaker than those c ultured for a shorter period. Many alpha(2)MRs were expressed when the neurons were likely to be extending the neurites well. From the devel opmental 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 n eurite promoting effect of alpha(2)M acts through alpha(2)M-alpha(2)MR binding and/or the following uptake of alpha(2)M.