ALPHA(2)-MACROGLOBULIN - A BINDING-PROTEIN FOR TRANSFORMING GROWTH-FACTOR-BETA AND VARIOUS CYTOKINES

alpha(2)-Macroglobulin (alpha(2)M) is a large plasma glycoprotein that has long been known as an irreversible inhibitor of a variety of prot einases. More recently, it has been reported that numerous growth fact ors, cytokines and hormones bind to alpha(2)M through diverse mechanis ms. We review here a series of observations from our laboratory that s upport the concept that alpha(2)M is a carrier protein for transformin g growth factor-beta (TGF-beta) and allows this factor to act as an au tocrine regulator of adrenocortical steroidogenic functions, alpha(2)M was found to be synthesized and secreted by primary cultures of bovin e adrenocortical cells in fairly large amounts (1 mu g/10(6) cells/24 h). TGF-beta is also secreted by this cell type, although under a late nt form. Two distinct latent TGF-beta complexes have been characterize d in adrenocortical cell conditioned medium, one of which is a complex between alpha(2)M and TGF-beta. Although alpha(2)M prevents the bindi ng of TGF-beta to its membrane receptors, long-term incubation of alph a(2)M with adrenocortical cells results in inhibition of cortisol prod uction similar to that observed in the presence of TGF-beta alone. Tak en together, these observations suggest that adrenocortical cells can release active TGF-beta from its latent complex with alpha(2)M through an unknown mechanism. alpha(2)M can therefore be considered as a TGF- beta carrier protein.