AN INHIBITOR OF PLATELET ADHESION TO ARTIFICIAL SURFACE

人造表面血小板粘附抑制剂

• 批准号: 3338259
• 负责人: SYED F MOHAMMAD
• 金额: $ 8.97万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1988-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3338259
• 关键词: antithrombogenic surface; arteriovenous shunt surgery; biological products; biomaterial interface interaction; blood donor; blood oxygenator; cardiovascular prosthesis; cardiovascular surgery; cell adhesion; clotting factor; enzyme linked immunosorbent assay; heart /lung bypass; hemodialysis; human subject; human tissue; immunoglobulin G; plasma; platelet aggregation inhibitors; polymers; prosthetic heart valve; radioimmunoassay; radiotracer; thrombosis; tissue /cell culture

Thrombosis and consumption of coagulation factors or formed elements of blood is often a consequence when blood comes in contact with a prosthetic device. Heparin and other pharmacologic agents are used to minimize these adverse reactions. In the absence of an ideal polymer that neither attracts blood cells nor activates clotting, several approaches have been taken to reduce adverse reactions when blood contacts a material. The applicants have demonstrated the presence of a unique albumin-immunoglobulin G complex (alb-IgG complex) in normal human serum. In an isolated state in vitro, this alb-IgG complex significantly inhibits the adhesion of platelets and adsorption of certain plasma proteins. Since surfaces coated with alb-IgG complex are less attractive to platelets, the applicants have proposed to carefully examine the effect of this protein complex on blood-material interaction. The specific aims include: attempts to develop better methods for purification of alb-IgG complex, and explore if this complex could be synthesized in vitro from albumin and IgG; develop a method for quantitation of alb-IgG complex and examine the concentration of this complex in normal serum and in patients whose blood is exposed to a large surface area of materials; and study the mechanism by which alb-IgG complex inhibits platelet adhesion. Affinity chromatographic techniques will be applied to evolve an efficient method for isolation and purification of alb-IgG complex from serum. Since albumin and IgG appear to be complexed via disulfide bond(s), thiol reagents will be used to explore possible synthesis of this complex. A synthetic alb-IgG complex with adhesion inhibitory property will be useful because investigators then do not have to depend on isolation and purification of this complex from serum in which it is present in small quantities (greater than 1 mg/ml). For quantitation of this complex in serum, an enzyme linked immunosorption assay (ELISA) will be developed; it is known that both albumin and IgG moieties in this complex react with their respective antibodies. Polymer surfaces coated with alb-IgG complex will be examined for their ability to attract platelets and leukocytes and their ability to initiate clotting at the blood-material interface; these experiments will be carried out in vitro with the help of a flow chamber and in ex vivo carotid-jugular Arterio-Venous shunt model in sheep. If surfaces coated with alb-IgG complex are found to be less thrombogenic, it may be possible to use this protein complex to improve the blood compatibility of prosthetic devices that contact blood.

血栓形成和凝血因子或形成元素的消耗 当血液接触到假肢时，血液通常是一种后果 设备。肝素和其他药理剂被用来最小化这些 不良反应。在没有理想聚合物的情况下 吸引血细胞也不能激活凝血，已经有几种方法 用来减少血液接触物质时的不良反应。这个 申请者展示了一种独特的 正常人血清中白蛋白-免疫球蛋白G复合体(Alb-Ig G复合体)。 在体外隔离状态下，这种alb-lgg复合体显著抑制 血小板的黏附和某些血浆蛋白的吸附。自.以来 涂有白蛋白-免疫球蛋白复合体的表面对血小板的吸引力较小 申请者提议仔细研究这种蛋白质的影响。 血液-物质相互作用的复杂性。具体目标包括： 试图开发更好的方法来纯化白蛋白-免疫球蛋白复合体，以及 探索白蛋白和免疫球蛋白能否在体外合成该复合体； 建立了白蛋白-免疫球蛋白复合体的定量方法，并检测了 正常血清和慢性阻塞性肺疾病患者血清中该复合体的浓度 暴露在较大的材料表面积中；并通过 哪种白蛋白-免疫球蛋白复合体抑制血小板黏附。亲和层析 将应用技术来发展一种有效的隔离和 从血清中纯化白蛋白-免疫球蛋白复合体。自从白蛋白和免疫球蛋白出现以来 要通过二硫键络合(S)，硫醇试剂将用于 探索合成该络合物的可能性。一种人工合成的白蛋白-免疫球蛋白复合物 具有黏附抑制特性将是有用的，因为研究人员 不需要依赖于从 少量存在的血清(大于1毫克/毫升)。 为了定量测定血清中的这一复合体，用酶联免疫吸附 将发展检测(ELISA)；已知白蛋白和免疫球蛋白 这个复合体中的部分与它们各自的抗体发生反应。高聚物 涂有白蛋白-免疫球蛋白复合体的表面将被检查其能力 吸引血小板和白细胞及其启动凝血的能力 血液-材料界面；这些实验将在 在流室的帮助下体外和在体颈总静脉 羊动静脉分流模型的建立。如果表面涂有白蛋白-免疫球蛋白 复合体被发现不那么容易血栓形成，可能使用这种方法 蛋白质复合体改善假体血液相容性的研究 接触血液的人。