Investigating the Effect of Bromelain on Leukocyte Recruitment Using Model Substr

描述(申请人提供)：炎症反应是一个高度调控的过程，涉及许多受体-配体相互作用，导致白细胞亚群向感染或损伤部位转移。炎症对健康和生存是必不可少的，但当它放松管制时，可能会导致各种疾病。全面了解白细胞募集的分子和多参数基础，对于开发同时针对多个受体-配体相互作用的更有效的治疗方法是至关重要的。此外，多参数方法对于研究现有和潜在的多靶点疗法对白细胞募集的影响将是有价值的。使用直接生物光刻方法，将产生14个呈现具有不同生物分子表面密度的相关配体的单组分和多组分模型底物，并用于白细胞流动分析。将揭示单个和多参数受体-配体相互作用对白细胞滚动和黏附的贡献，并将研究菠萝蛋白酶(一种天然抗炎蛋白酶制剂)8对不同白细胞亚群滚动和黏附的影响。 与公共健康相关：将应用光化学方法产生表面固定的生物分子梯度，用于研究白细胞募集的分子基础，并揭示一种替代药物抗炎治疗的作用机制。这些研究将为开发治疗炎症性疾病的多靶点疗法奠定基础。

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.