IMMUNOLOGY OF HUMAN PLATELETS (HIV-1-ITP)

人类血小板的免疫学 (HIV-1-ITP)

• 批准号: 7118014
• 负责人: SIMON KARPATKIN
• 金额: $ 33.01万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7118014
• 关键词: HIV infections; NAD(P)H dehydrogenase; autoantibody; clinical research; cytolysis; flow cytometry; free radicals; genetically modified animals; granulocyte; human tissue; hydrogen peroxide; immune complex; immunohematology; laboratory mouse; leukotrienes; lipoxygenase; macrophage; platelet disorder; platelets; shear stress; thrombocytopenia

DESCRIPTION (provided by applicant): We have discovered a novel mechanism for platelet lysis and clearance in HIV-I-ITP patients, which is complement independent and induced by H202/free radicals. The Ab is directed against an immunodominant platelet GPIIla49-66 epitope and sequestered within serum immune complexes. Other Ab's against GPIIla do not have this effect. A rabbit Ab raised against GPIIla49-66 has the same effect. The mechanism of H202/free radical induction is via an apparent NADPH oxidase pathway in platelets since it is inoperative in NADPH oxidase deficient mice (p47phox(-/-) and gp91phox(-/-)) and dependent upon a functioning platelet 12-1ipoxygenase. I. Analyze the Presence of a Functioning NADPH Oxidase Pathway in Platelets. 2. Analyze the Mechanism of the Requirement of Platelet 12-Lipoxygenase for Ab-induced Platelet fragmentation. 3. Determine whether NADPH oxidase/ROS induced platelet fragmentation is a unique effect of anti- GPIIla49-66 Ab in HIV-I-ITP patients or a general mechanism for other platelet destructive disorders. 4. Determine whether anti-GPIIla49-66 is a result of molecular mimicry with antigen of infectious origin or its products.

描述(申请人提供)：我们在HIV-I-ITP患者中发现了一种新的血小板溶解和清除机制，该机制不依赖补体，由H202/自由基诱导。该抗体针对免疫优势的血小板GPIIla49-66表位，并隔离在血清免疫复合体中。其他抗GPIIla的抗体则没有这种作用。兔抗GPIIla49-66抗体也有同样的效果。H202/自由基的诱导机制是通过血小板中明显的NADPH氧化酶途径，因为它在NADPH氧化酶缺陷小鼠(p47Phox(-/-)和gp91Phox(-/-))中不起作用，并依赖于功能正常的血小板12-1环氧合酶。分析血小板中是否存在功能正常的NADPH氧化酶途径。2.分析了单抗诱导的血小板碎裂对血小板12-脂氧合酶的需求机制。3.确定NADPH氧化酶/ROS诱导的血小板碎裂是抗GPIIla49-66抗体在HIV-I-ITP患者中的独特作用还是其他血小板破坏性疾病的一般机制。4.确定抗GPIIla49-66是否是感染性抗原或其产物的分子模拟的结果。