IMPACT OF SELECTIN DENSITY ON MONOCYTE ADHESION STRENGTH

选择素密度对单核细胞粘附强度的影响

• 批准号: 7954818
• 负责人: ELIAS BOTVINICK
• 金额: $ 0.3万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954818
• 关键词: Adhesions; Animals; Autoimmune Diseases; Binding; Biotechnology; Chronic; Collaborations; Colloids; Computer Retrieval of Information on Scientific Projects Database; Dextrans; Diffusion; Dose; Endothelial Cells; Foreign Bodies; Funding; Grant; Healed; Immune response; In Vitro; Inflammation; Inflammatory; Inflammatory Response; Institution; Knowledge; Lasers; Lead; Leukocytes; Ligands; Lymphocyte; Measurement; Measures; Membrane; Natural regeneration; Nature; Pathologic Processes; Peptides; Phagocytosis; Physiological; Research; Research Personnel; Resources; Selectins; Source; Surface; Technology; Therapeutic; Tissues; Trauma; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; United States National Institutes of Health; Vascular Endothelial Cell; cell injury; density; dextran; dosage; healing; in vivo; injured; macrophage; migration; monocyte; neutrophil; parent grant; pathogen; physical property; prototype; receptor; research study; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Inflammation is classified as a physiological response to suppress pathological processes. This response is highly localized to literally destroy injured tissues, pathogens, etc and promote tissue healing/regeneration [1] Chronic inflammation can also lead to pathological immune responses, e.g. autoimmune diseases, and therefore therapies that suppress systemic inflammation would be beneficial[2]. Receptor-ligand interactions are critical for every step of an inflammatory response including neutrophil, monocyte, lymphocyte, and macrophage adhesion to vascular endothelial cells, transvascular migration (diapedesis) into inflamed tissues, and phagocytosis of foreign bodies, injured tissues, pathogens, etc. The objective of the parent grant is to develop a dextran-peptide conjugate that selectively binds injured tissue surfaces to form a protective colloid barrier against trauma-induced inflammatory cell damage to healthy tissues. Dr. Bowen has developed an e-selectin-binding dextran-peptide bioconjugate that has been shown to effectively inhibit monocyte adhesion to endothelial cells grown in culture that have been stimulated by tumor necrosis factor-¿ (TNF-¿)- (see preliminary results). A specific aim of the parent grant is to assess the effects of bioconjugate treatment on leukocyte adhesion to cultured endothelial cells subjected to physiological flow. In order to measure physical properties of e-selectin binding therapeutics, an in vitro experiment has been developed where cultured monocytes bind to substrates containing various densities of purified e-selectin. These measurements are made to understand the nature of the bioconjugate without confounding effects introduced by the endothelial cell such as internalization and membrane diffusion. In this collaboration we will use the 3-axis force clamp of the Spatially Modulated Microbeam (SMM) LAMMP core technology. We will measure the adhesion strength between monocytes and substrates coated with varying densities of e-selectin. We will first determine the relationship between e-selectin density and adhesion strength, and then determine the dosage of the dextran bioconjugate required to block monocyte adhesion to a substrate with varying densities of e-selectin. Results from this collaboration will provide fundamental knowledge of molecular interactions between monocyte and endothelial cell ligands as well as between prototype-bioconjugates and endothelial cell ligands. This information will be used to formulate dosing in in vivo animals studies.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 炎症被归类为对抑制病理过程的物理反应。这种反应高度定位于实际破坏的受伤组织，病原体等，并促进组织愈合/再生[1]慢性感染也会导致病理免疫调查，例如自身免疫性疾病，因此抑制全身感染的疗法将是有益的[2]。受体配体相互作用对于炎症反应的每个步骤至关重要 父授予的目的是开发一种葡聚糖肽结合物，该葡萄肽有选择地结合受伤的组织表面，形成受保护的胶体屏障，以抗创伤引起的炎症细胞对健康组织的损害。 Bowen博士已经开发了一种E-选择蛋白结合葡萄糖肽生物偶联物，该二轭物已被证明可以有效抑制单核细胞粘合剂对培养物中生长的内皮细胞的粘合剂，这些细胞已受到肿瘤坏死因子 - （TNF--）的刺激（TNF-） - （请参阅初步结果）。父母赠款的一个具体目的是评估生物缀合物治疗对白细胞遵守受物理流量培养的内皮细胞的影响。为了测量E-选择素结合疗法的物理特性，已经开发了一个体外实验，其中培养的单核细胞与含有各种纯化E-选择素密度的底物结合。这些测量是为了理解生物偶联物的性质，而没有内皮细胞引入的混淆效应，例如内在化和膜扩散。 在这项合作中，我们将使用空间调制的微束（SMM）LAMMP核心技术的3轴力夹。我们将测量单核细胞和涂有不同E-选择素密度的底物之间的粘合强度。我们将首先确定E-选择蛋白密度和粘合强度之间的关系，然后确定需要将单核细胞粘合剂阻塞到具有不同密度E-链克蛋白的底物所需的葡聚糖生物偶联物的剂量。这种合作的结果将提供单核细胞和内皮细胞配体之间的分子相互作用，以及原型 - 双缀合物和内皮细胞配体之间的基本知识。该信息将用于在体内动物研究中制定剂量。