In vitro nerve-growth-promoting activity of human plasma alpha 1-acid glycoprotein

Human plasma alpha 1-acid glycoprotein or orosomucoid (OR), and its derivatives, prepared by sequential enzymatic cleavage of the carbohydrate units, were tested for their nerve-growth-promoting activities with explants of whole dorsal root ganglia from chick embryos. The results showed that the OR derivatives with terminal galactose, N-acetylglucosamine, or mannose have marked neurite-promoting activities. These preparations at a concentration of 100 micrograms/ml are equivalent to 5% fetal bovine serum (protein concentration 3,000 micrograms/ml) in their ability to elicit extensive neurite outgrowth and collateral branching. The asialo-OR, or ASOR, is the most potent form: its activity is estimated to be 20 times higher than that of transferrin and 100 times over that of fibronectin; it is approximately 1/1,500 that of NGF. The neurite-promoting activity of OR is independent of the non-neuronal cells and their products and can be blocked by a specific antiserum against OR. The mode of action of OR on the in vitro nerve growth is discussed and the pathophysiological significance of this plasma glycoprotein is considered in light of data from recent clinical and pathological studies.