Investigating the Effect of Bromelain on Leukocyte Recruitment Using Model Substr

使用模型 Substr 研究菠萝蛋白酶对白细胞募集的影响

• 批准号: 8196293
• 负责人: Christine Toh Herman
• 金额: $ 4.14万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-16 至 2012-08-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8196293
• 关键词: Action Potentials; Adhesions; Adhesives; Alternative Medicine; Anti-Inflammatory Agents; Anti-inflammatory; Biological Assay; Blood Vessels; Cell surface; Data; Development; Disease; E-Selectin; Endothelial Cells; Generations; Health; Immune response; In Vitro; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Injury; Integrins; Intercellular Adhesion Molecules; Investigation; Lead; Left; Leukocyte Rolling; Leukocyte Trafficking; Leukocytes; Ligands; Lymphocyte Activation; Mediating; Methods; Modeling; Molecular; P-Selectin; P-selectin ligand protein; Peptide Hydrolases; Pharmaceutical Preparations; Preparation; Process; Proteins; Selectins; Site; Substrate Interaction; Surface; Therapeutic; Work; base; chemokine; computerized data processing; density; monolayer; public health relevance; receptor; response; shear stress; therapeutic target

DESCRIPTION (provided by applicant): The inflammatory response is a highly regulated process involving numerous receptor-ligand interactions that result in the trafficking of leukocyte subsets to sites of infection or injury. Inflammation is essential for health and survival, but a variety of diseases can result when it becomes deregulated. A comprehensive understanding of the molecular and multi-parametric basis of leukocyte recruitment is essential for the development of more effective therapeutics that target multiple receptor-ligand interactions simultaneously. Additionally, a multi-parameter approach would be valuable for investigating the effects of existing and potential multi-target therapeutics on leukocyte recruitment. Using a direct biophotolithographic approach, 14 single- and multi-component model substrates presenting relevant ligands with varied biomolecular surface densities will be generated and used in leukocyte flow assays. The contributions of individual and multi- parameter receptor-ligand interactions to leukocyte rolling and adhesion will be revealed, and the effect of bromelain (a natural anti-inflammatory proteinase preparation) eight on the rolling and adhesion of various subsets of leukocytes will be investigated. PUBLIC HEALTH RELEVANCE: A photochemical approach will be applied to the generation of surface-immobilized biomolecular gradients that will be utilized to investigate the molecular basis of leukocyte recruitment and reveal the mechanism of action of an alternative medicine anti-inflammatory treatment. These studies will lay the groundwork for the development of multi-target therapeutics for the treatment of inflammatory diseases.

描述（由申请人提供）：炎症反应是一个高度调节的过程，涉及许多受体 - 配体相互作用，导致白细胞亚群运输到感染或受伤部位。炎症对于健康和生存至关重要，但是当炎症引起管制时可能会导致多种疾病。 对白细胞募集的分子和多参数基础的全面理解对于开发更有效的治疗剂至关重要，这些治疗剂同时针对多种受体配体相互作用。 此外，多参数方法对于研究现有和潜在的多目标治疗剂对白细胞募集的影响很有价值。使用直接的生物光谱方法，将生成并在白细胞流量测定法中生成14个具有不同生物分子表面密度的相关配体的单组和多组分模型底物。将揭示个体和多参数受体 - 配体相互作用对白细胞滚动和粘附的贡献，将研究溴烯（一种天然的抗炎蛋白酶制备）对白血细胞各种亚群的滚动和粘附的影响。 公共卫生相关性：将采用光化学方法来生成表面涂成的生物分子梯度，该梯度将用于研究白细胞募集的分子基础，并揭示了替代药物抗炎治疗的作用机理。这些研究将为开发多目标治疗剂的炎症性疾病的发展奠定基础。