Inhibition of platelet aggregation by native and desialised alpha-1 acid glycoprotein

Abstract

The alpha-1 acid glycoprotein (orosomucoid; AAG) is a normal constituent of human plasma (650±215 µg ml⁻¹) which increases in concentration as much as fivefold in association with acute inflammation and cancer, and thus is recognised as an acute phase protein^1,2. AAG consists of a single polypeptide chain, has a molecular weight of 44,100, and contains ∼45% carbohydrate including 12% sialic acid; it is the most negatively charged of the plasma proteins³. Certain of the biological properties of AAG are related to its sialic acid content^1,3; thus, clearance and immunogenicity of AAG are markedly increased on desialisation^4,5. The biological functions of AAG are largely unknown. AAG has the ability to inhibit certain lymphocyte reactivities including blastogenesis in response to concanavalin A, phytohaemagglutinin and allogeneic cells⁶, and these inhibitory effects are enhanced in association with desialisation⁷. In view of these observations, a report that unphysiologically large (5–15 mg ml⁻¹) amounts of AAG inhibit the platelet aggregation induced by ADP and adrenaline⁸, and evidence that a sialic acid-deficient species of AAG appears elevated in several chronic disease states^9,10, we compared the effects of AAG and its desialised counterpart (AAG-D) on platelet aggregation. We report that desialisation of AAG is associated with increased expression of activity inhibitory to the platelet aggregation otherwise observed on stimulation with ADP, collagen or thrombin.