Adnesion Receptors of the Insect Immune System

昆虫免疫系统的粘附受体

• 批准号: 6370392
• 负责人: JAMES B NARDI
• 金额: $ 26.15万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-15 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6370392
• 关键词: Insecta; Manduca; antigen antibody reaction; cell adhesion; cell adhesion molecules; cell aggregation; cell capsule; cell cell interaction; immunocytochemistry; membrane proteins; molecular cloning; molecular shape; polymerase chain reaction; protein structure function; receptor expression; thrombospondins

DESCRIPTION (provided by the applicant): Upon encountering objects that they recognize as foreign, a primary response of the cells (hemocytes) of the insect immune system is their aggregation in multiple layers on the surfaces of the foreign object in a process known as encapsulation. As the initiation of aggregation and encapsulation occurs, hemocytes switch from their usual nonadherent state to an adherent state and begin expressing new adhesion proteins that orchestrate the encapsulation process. Many pathogens and parasites, however, are able to circumvent this host defense of insects by either preventing or suppressing the expression of adhesion receptors. Although a great variety of adhesion receptors are known to be involved in the interactions of cells in the mammnalian immune system, no comparable receptors involved in regulating encapsulation are yet known for insects. To establish the role of adhesion receptors in the insect immune response, this study will proceed by several routes using the large, well-studied moth Manduca sexta. Three groups of proteins implicated in plasmatocyte adhesion and encapsulation will be investigated. (1) The function of the granular cell-specific protein lacunin in adhesion of plasmatocytes will be tested. This multidomain protein is present in capsules at the interface between the foreign surface and the adherent plasmatocytes. Experiments will test the role of the thrombospondin domains of lacunin in plasmatocyte adhesion. (2) The function of insect cell adhesion proteins from the immunoglobulin superfamily in hemocyte encapsulation will be investigated. Recombinant proteins representing the putative adhesive domains of three surface proteins having iminunoglobulin-like domains as well as antibodies generated to these surface proteins will be assayed for their effects on aggregation and encapsulation of hemocytes. (3) Two plasmatocyte integral membrane proteins, which function in encapsulation, will be characterized. Monoclonal antibodies against these surface proteins disrupt plasmatocyte aggregation. and encapsulation. These monoclonal antibodies were used to affinity purify the proteins for partial sequencing. With information now available on the partial sequences of several peptides from each protein, probes will be generated for screening of a hemocyte cDNA library and obtaining their complete sequences, which should reveal additional features of these adhesion receptors. Understanding the molecular underpinnings of the insect immune response will clearly help in understanding the fate of pathogens in the blood of insect vectors of human diseases.

描述（由申请人提供）：当他们遇到物体时 识别为外来物，昆虫细胞（血细胞）的主要反应 免疫系统是它们在物体表面的多层聚集 外来对象的过程称为封装。作为发起 发生聚集和封装，血细胞从平常的状态转变为 非粘附状态到粘附状态并开始表达新的粘附 协调封装过程的蛋白质。许多病原体和 然而，寄生虫能够通过以下方式绕过昆虫的这种宿主防御： 防止或抑制粘附受体的表达。 尽管已知有多种粘附受体参与 哺乳动物免疫系统中细胞的相互作用，没有类似的受体 昆虫中参与调节包囊的机制尚不清楚。建立 粘附受体在昆虫免疫反应中的作用，本研究将 使用经过充分研究的大型蛾 Manduca sexta 沿着几条路线前进。 与浆细胞粘附和封装有关的三组蛋白质 将被调查。 (1)颗粒细胞特异性蛋白的功能 将测试浆细胞粘附中的lacunin。这种多结构域蛋白 存在于胶囊中异物表面和内含物之间的界面处 贴壁浆细胞。实验将测试血小板反应蛋白的作用 浆细胞粘附中的腔隙蛋白结构域。 (2)昆虫细胞的功能 血细胞封装中免疫球蛋白超家族的粘附蛋白 将被调查。代表假定粘合剂的重组蛋白 三种表面蛋白的结构域也具有免疫球蛋白样结构域 因为针对这些表面蛋白产生的抗体将被检测其 对血细胞聚集和封装的影响。 (3)浆细胞2个 具有封装功能的整合膜蛋白将被 特点。针对这些表面蛋白的单克隆抗体会破坏 浆细胞聚集。和封装。这些单克隆抗体是 用于亲和纯化蛋白质以进行部分测序。有资料 现在可以获取每种蛋白质的几种肽的部分序列， 将生成探针用于筛选血细胞 cDNA 文库并获得 它们的完整序列，应该揭示这些的附加特征 粘附受体。 了解昆虫免疫反应的分子基础将 明显有助于了解昆虫血液中病原体的命运 人类疾病的媒介。