Preclinical investigations of alpha(1)-acid glycoprotein (orosomucoid)

The molecular properties of alpha(1)-acid glycoprotein are briefly discusse d. This molecule has been shown in in vitro experiments to have both a stab ilizing effect on vascular permeability and antiinflammatory properties. We were able to demonstrate these two effects in vivo in guinea pigs (skin, E van's Blue extravasation) and in rats (paw, carrageenan induced inflammatio n). Further experiments were performed in rats relating to possible therape utic indications for alpha(1)-acid glycoprotein: (1) inhibitory effect on b rain edema formation after experimental stroke, (2) therapeutic effect in t he puromycin aminonucleoside-induced minimal change nephrosis, (3) improvem ent of vital parameters in hemorrhagic-hypovolemic shock, (4) increase in s urvival rate in septic peritonitis, and (5) promising effects in burn-induc ed remote lung injury. The high content of sialic acid and the high negative charge of alpha(1)-ac id glycoprotein are believed to be major contributors to its stabilizing ef fect on vascular permeability. The protein is bound to the glycocalyx of th e endothelial cells (and presumably to structures of the glomerular basemen t membrane), thereby hindering the passage of other polyanionic molecules t hrough the vascular wall. The antiinflammatory/immunomodulatory effect of alpha(1)-acid glycoprotein appears mainly due to suppression of polymorphonuclear neutrophils. This ac tion is dependent on the glycan part of the molecule, which is highly varia ble (microheterogeneity). It is obvious that there are differences between the different glycan forms as far as the antiinflammatory property of the p rotein is concerned. Together with data in the literature, the results presented here suggest a variety of potential indications for therapeutic use of al-acid glycoprotei n in humans.