EOSINOPHIL MAJOR BASIC PROTEIN IN HUMAN PREGNANCY

人类妊娠期的嗜酸性粒细胞主要碱性蛋白

• 批准号: 3322870
• 负责人: Gerald J Gleich
• 金额: $ 15.94万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1992-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3322870
• 关键词: affinity chromatography; aminoacid analyzer; autoradiography; birth; blood chemistry; blood proteins; eclampsia; eosinophil; gel electrophoresis; gestational diabetes mellitus; high performance liquid chromatography; human pregnant subject; human subject; laboratory mouse; patient care management; placenta; pregnancy disorder; pregnancy toxemia /hypertension; premature labor; prenatal diagnosis; protein structure; radioimmunoassay; spontaneous abortion; trophoblast; urinalysis

Prior studies have shown that the eosinophil granule contains an intensely cationic proteinaceous molecule termed the major basic protein (gMBP). Guinea pig MBP accounts for over 50% of granule proteins and 25% of the total cellular protein. gMBP is localized to the core of the granule and exists there as a crystal. gMBP has also been identified in the human; both guinea pig and human gMBP are potent toxins to helminths and mammalian cells; and gMBP has been proposed as a mediator of pathological damage in bronchial asthma and other inflammatory diseases. During studies of the role of gMBP in hypersensitivity diseases, we found that elevated levels of gMBP are present in human pregnancy. MBP levels rise shortly after conception, plateau at about 20 weeks and show a late rise shortly before labor. The pregnancy-associated major basic protein (pMBP) behaves identically to gMBP in its immunochemical properties, but initial studies showed a difference in molecular weight. In recent studies, we have found that a late rise in pMBP levels is associated with human labor. In this proposal, we outline studies, first, to purify pMBP from placenta in quantities sufficient for chemical analyses. Second, we will test whether purified pMBP is identical to gMBP. These experiments are predicted on our ability to purify pMBP and on prior physicochemical information concerning gMBP. Third, we will measure levels of serum pMBP throughout human pregnancy in 100 normal pregnant women and in a control group of 30 nonpregnant women. And fourth, we will measure serum pMBP levels in various pathological conditions associated with pregnancy, including tests of the hypothesis that elevations of pMBP before 36 weeks predict premature labor. We also will test whether pMBP is useful in the management of prolonged pregnancy and whether a subset of patients with recurrent abortions may have abnormalities in the plasma levels of pMBP. Overall, these experiments will determine whether spontaneous labor can be predicted by late rises in pMBP and they offer the hope of obtaining new information concerning the function in human pregnancy of the relatively neglected trophoblast known as the X cell.

先前的研究表明，嗜酸性粒细胞颗粒含有 强阳离子蛋白质分子，称为主要碱性分子 蛋白质（gMBP）。 豚鼠MBP占50%以上 颗粒蛋白和细胞总蛋白的25%。 gMBP 是 位于颗粒的核心并以晶体形式存在。 gMBP 也已在人体中得到鉴定；豚鼠和 人类 gMBP 对蠕虫和哺乳动物细胞具有强效毒素； gMBP 已被提议作为病理学的调节剂 支气管哮喘和其他炎症性疾病的损害。 在研究 gMBP 在过敏性疾病中的作用时， 我们发现人类体内的 gMBP 水平升高 怀孕。 MBP 水平在受孕后不久上升，稳定在 大约 20 周，在临产前不久出现晚期升高。 这 妊娠相关主要碱性蛋白 (pMBP) 的行为 其免疫化学特性与 gMBP 相同，但最初 研究表明分子量存在差异。 近来 研究发现，pMBP 水平后期升高是 与人类劳动有关。 在本提案中，我们首先概述了从其中纯化 pMBP 的研究 胎盘的数量足以进行化学分析。 第二， 我们将测试纯化的 pMBP 是否与 gMBP 相同。 这些 实验预测我们纯化 pMBP 的能力 有关 gMBP 的先前理化信息。 第三，我们 将测量人类妊娠期间血清 pMBP 的水平 100 名正常孕妇和 30 名对照组 非孕妇。 第四，我们将测量血清 pMBP 与各种病理状况相关的水平 怀孕，包括检验以下假设： 36 周前的 pMBP 预测早产。 我们也会测试 pMBP 是否有助于长期治疗 妊娠以及是否有一部分患者复发 流产可能导致血浆 pMBP 水平异常。 总的来说，这些实验将确定是否自发 分娩可以通过 pMBP 的后期升高来预测，并且它们提供了 希望获得有关该功能的新信息 人类怀孕时相对被忽视的滋养层称为 X 细胞。