Feige J J, Negoescu A, Keramidas M, Souchelnitskiy S, Chambaz E M
CEA, Biochimie des Régulations Cellulaires Endocrine, INSERM Unité 244, Département de Biologie Moléculaire et Structurale, Grenoble, France.
Horm Res. 1996;45(3-5):227-32. doi: 10.1159/000184793.
alpha 2-Macroglobulin (alpha 2M) is a large plasma glycoprotein that has long been known as an irreversible inhibitor of a variety of proteinases. More recently, it has been reported that numerous growth factors, cytokines and hormones bind to alpha 2M through diverse mechanisms. We review here a series of observations from our laboratory that support the concept that alpha 2M is a carrier protein for transforming growth factor-beta (TGF-beta) and allows this factor to act as an autocrine regulator of adrenocortical steroidogenic functions. alpha 2M was found to by synthesized and secreted by primary cultures of bovine adrenocortical cells in fairly large amounts (1 microgram/10(6) cells/24 h). TGF-beta is also secreted by this cell type, although under a latent form. Two distinct latent TGF-beta complexes have been characterized in adrenocortical cell conditioned medium, one of which is a complex between alpha 2M and TGF-beta. Although alpha 2M prevents the binding of TGF-beta to its membrane receptors, long-term incubation of alpha 2M with adrenocortical cells results in inhibition of cortisol production similar to that observed in the presence of TGF-beta alone. Taken together, these observations suggest that adrenocortical cells can release active TGF-beta from its latent complex with alpha 2M through an unknown mechanism. alpha 2M can therefore be considered as a TGF-beta carrier protein.
α2-巨球蛋白（α2M）是一种大型血浆糖蛋白，长期以来一直被认为是多种蛋白酶的不可逆抑制剂。最近，有报道称许多生长因子、细胞因子和激素通过多种机制与α2M结合。我们在此回顾我们实验室的一系列观察结果，这些结果支持以下概念：α2M是转化生长因子-β（TGF-β）的载体蛋白，并使该因子能够作为肾上腺皮质类固醇生成功能的自分泌调节因子发挥作用。发现α2M由牛肾上腺皮质细胞原代培养物大量合成并分泌（1微克/10^6个细胞/24小时）。TGF-β也由这种细胞类型分泌，尽管是以潜伏形式。在肾上腺皮质细胞条件培养基中已鉴定出两种不同的潜伏TGF-β复合物，其中一种是α2M与TGF-β之间的复合物。虽然α2M可阻止TGF-β与其膜受体结合，但α2M与肾上腺皮质细胞长期孵育会导致皮质醇生成受到抑制，这与单独存在TGF-β时观察到的情况相似。综上所述，这些观察结果表明，肾上腺皮质细胞可以通过一种未知机制从其与α2M的潜伏复合物中释放出活性TGF-β。因此，α2M可被视为一种TGF-β载体蛋白。
