Investigating the Effect of Bromelain on Leukocyte Recruitment Using Model Substr

描述（由申请人提供）：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，导致白细胞亚群运输到感染或损伤部位。炎症对健康和生存至关重要，但当它失去控制时，各种疾病就会产生。全面了解白细胞募集的分子和多参数基础对于开发更有效的治疗方法至关重要，这些治疗方法可以同时靶向多种受体-配体相互作用。此外，多参数方法对于研究现有和潜在的多靶点治疗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，将生成14种单组分和多组分模型底物，这些底物具有不同生物分子表面密度的相关配体，并用于白细胞流分析。将揭示单个和多参数受体-配体相互作用对白细胞滚动和粘附的贡献，并研究菠萝蛋白酶（一种天然抗炎蛋白酶制剂）8对各种白细胞亚群滚动和粘附的影响。

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.