Inhibition of platelet aggregation by native and desialised alpha-1 acid glycoprotein
Inhibition of platelet aggregation by native and desialised alpha-1 acid glycoprotein
复制标题
天然和脱唾液酸 α-1 酸性糖蛋白抑制血小板聚集
作者：
M. Costello;B. Fiedel;H. Gewurz
α-1酸性糖蛋白(−1)是人体血浆的正常成分(650ugmlAAG)，与急性炎症和癌症有关，其浓度增加五倍，因此被认为是急性时相蛋白1。AAG由单一多肽链组成，分子量为44,100，含有∼45%的碳水化合物，包括12%的唾液酸；它是血浆蛋白中负电荷最大的蛋白3。AAG的某些生物学性质与其唾液酸含量1，3有关；因此，AAG的清除性和免疫原性在需要4，5时显著增加。AAG的生物学功能在很大程度上是未知的。AAG具有抑制某些淋巴细胞反应的能力，包括对刀豆蛋白A、植物血凝素和同种异体细胞的反应6，这些抑制作用随着愿望的增强而增强。鉴于这些观察，有报道称非生理性大剂量(5-15mgmlAAG 1)抑制由腺苷二磷酸和肾上腺素8诱导的血小板聚集，并且有证据表明一种唾液酸缺乏的AAG在几个慢性病状态中似乎升高9，10，我们比较了AAG和其理想的对应物(−-D)对血小板聚集的影响。我们报道，AAG的消退与ADP、胶原或凝血酶刺激时对血小板聚集的抑制活性的增加有关。
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 protein1,2. 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 content1,3; thus, clearance and immunogenicity of AAG are markedly increased on desialisation4,5. 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 states9,10, 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.