TRANSPLACENTAL PASSAGE OF HIV AND IMMUNOGLOBULIN

HIV 和免疫球蛋白的经胎盘传递

• 批准号: 2067177
• 负责人: Arye Rubenstein
• 金额: $ 16.66万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2067177
• 关键词: AIDS; HIV infections; communicable disease transmission; congenital infection; embryo /fetus; female; human immunodeficiency virus; human pregnant subject; human subject; immune complex; immunoglobulin G; immunoglobulin isotypes; perfusion; placental transfer; pregnancy circulation

DESCRIPTION: (Adapted from the author's abstract.) The reported incidence of pre- and perinatal transmission of HIV from an infected mother to the infant ranges from 30% to 50%. Although some evidence indicates that transplacental transfer of HIV can occur early in gestation, the precise mechanism by which maternal HIV transits the placenta is not known. The human placental "barrier," a fetally-derived organ which is the interface between maternal and fetal vascular systems, has been shown to be permeable to both cellular and soluble maternal elements. Transplacental transfer of HIV almost certainly occurs at the maternal-fetal vascular interface, where maternal blood bathes the fetal placental tissues. The placental cells that compose the lobular fetal cotyledons are themselves susceptible to HIV infection by virtue of both their location at the maternal-fetal interface and by their cell surface properties. Further, trophoblastic cells express Fc receptors for immunoglobulin and surface CD4. Fc receptors, functioning in transplacental transport of maternal immunoglobulin to the fetus, could also mediate transfer of HIV complexed with maternal anti-HlV IgG, or result in the enhancement of HIV infection of placental cells bearing Fc receptors. Certain observations should be noted: (a) the presence of HIV antigen in Fc receptor-bearing, CD4-positive Hofbauer cells has been demonstrated in the placenta in an HIV-positive pregnancy; (b) growth in different cell types has been shown to alter HIV tropism, thus influencing viral cytopathogenicity; (c) the effect of HIV passage through placental cells is not known but it may influence HIV tropism for fetal cell sub-populations; (d) infants infected in utero have a high incidence of multi-organ-system involvement as well as of immunologic dysfunction; and (e) the isolated perfused human placental cotyledon (IPC) has been used as a model to study transplacental transfer of soluble metabolites and drugs since 1967 and was used recently to evaluate transplacental transfer of zidovudine (AZT). Accordingly, the Principal Investigator proposes to use the IPC in novel investigations in order to delineate transplacental passage of HIV, immunoglobulins, and HIV:anti-HIV IgG complexes. She and her research associates will: (1) determine the efficiency of transplacental transfer of free virions and HIV-infected autologous maternal leukocytes in order and will quantify infected cells in the fetal circulation; (2) determine directly the relative efficiency of the transplacental passage of immunoglobulin of defined class and subclass, from the maternal circulation to the fetal circulation; and (3) localize the deposition of HIV:anti-HIV IgG complexes in the perfused placental lobule and investigate the potential enhancement of placental monocyte infection by HIV:IgG complexes, monitoring thereby immune complex-induced placental pathology.

摘要：（改编自作者的摘要）报告发病率 艾滋病毒在产前和围产期从受感染的母亲传播给 婴儿的比例在30%到50%之间。 尽管有证据表明， 艾滋病毒的经胎盘转移可发生在妊娠早期， 母体HIV通过胎盘的机制尚不清楚。 的 人胎盘“屏障”，一种胎儿衍生的器官， 在母体和胎儿血管系统之间， 与细胞和可溶性母体元素有关。 经胎盘转移 HIV几乎肯定发生在母胎血管界面， 母体血液浸泡胎儿胎盘组织。 胎盘细胞 组成小叶胎儿子叶的细胞本身也容易感染艾滋病病毒 由于它们位于母胎界面， 和细胞表面的特性。 此外，滋养层细胞表达 免疫球蛋白和表面CD 4的Fc受体。 Fc受体，功能性 在母体免疫球蛋白经胎盘转运到胎儿中， 还介导与母体抗HIV IgG复合的HIV转移，或 导致携带Fc的胎盘细胞的HIV感染增强 受体。 应注意的某些情况是：（a）艾滋病毒的存在 在Fc受体携带的，CD 4阳性的Hofbauer细胞中的抗原已经被 在HIV阳性妊娠的胎盘中证实;（B） 不同的细胞类型已被证明可以改变HIV的嗜性，从而影响 病毒致细胞病变性;（c）HIV通过胎盘的影响 细胞是未知的，但它可能会影响艾滋病毒对胎儿细胞的嗜性 （d）在子宫内感染的婴儿， 多器官系统受累以及免疫功能障碍;以及 (e)分离的灌注的人胎盘子叶（IPC）已被用作 研究可溶性代谢物和药物经胎盘转运的模型 自1967年以来，最近被用来评估经胎盘转移的 齐多夫定（AZT）。 因此，主要研究者建议使用 新研究中的IPC，以描述经胎盘 HIV、免疫球蛋白和HIV：抗HIV IgG复合物的传代。 她和 她的研究伙伴将：（1）确定效率 游离病毒粒子和HIV感染的自体 母体白细胞，并将量化胎儿中的感染细胞 （2）直接确定相对效率; 确定的类别和亚类的免疫球蛋白的经胎盘通过， 从母体循环到胎儿循环;（3）定位 HIV：抗HIV IgG复合物在胎盘中的沉积 小叶，并探讨胎盘单核细胞的潜在增强 HIV感染：IgG复合物，监测由此引起的免疫复合物 胎盘病理学