Inhibition of platelet aggregation by native and desialised alpha-1 acid glycoprotein.
The alpha-1 acid glycoprotein (orosomucoid; AAG) is a normal constituent of human plasma (650+/-215 microgram ml(-1)) which increases in concentration as much as fivefold in associations with acute inflammation and cancer, and thus is recognized as an acute phase protein. AAG consists of a single polypeptide chain, has a molecular weight of 44,100, and contains approximately 45% carbohydrate including 12% sialic acid; it is the most negatively charged of the plasma proteins. Certain of the biological properties of AAG are related to its sialic acid content; thus, clearance and immunogenicity of AAG are markedly increased on desialisation. The biological functions of AAG are largely unknown. AAG has the ability to inhibit certain lymphocyte re-activities including blastogenesis in response to concanavalin A, phytohaemagglutinin and allogeneic cells, and these inhibitory effects are enhanced in association with desialisation. 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 adrenaline, and evidence that a sialic acid-deficient species of AAG appears elevated in several chronic disease states, 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.
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D003094:Collagen / Q000037:antagonists & inhibitors; D006801:Humans; D009961:Orosomucoid / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D012794:Sialic Acids / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors
D009961:Orosomucoid; D012794:Sialic Acids; D000244:Adenosine Diphosphate; D003094:Collagen; D013917:Thrombin