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.
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.
|Banks, Jessica M; Herman, Christine T; Bailey, Ryan C (2013) Bromelain decreases neutrophil interactions with P-selectin, but not E-selectin, in vitro by proteolytic cleavage of P-selectin glycoprotein ligand-1. PLoS One 8:e78988|
|Herman, Christine T; Potts, Gregory K; Michael, Madeline C et al. (2011) Probing dynamic cell-substrate interactions using photochemically generated surface-immobilized gradients: application to selectin-mediated leukocyte rolling. Integr Biol (Camb) 3:779-91|