(649d) Analysis of Neutrophil Migration in Response to Complex Gradients Using Microfluidic Platforms

Neutrophil constitute the largest class of white blood cells and are the front line of cellular immune defense. They are able to sense and migrate upstream of concentration gradients of chemo-attractants in search of primary sites of inflammation in a process termed chemotaxis. These chemo-attractants include formylated peptides, complement, and various chemokines. Each chemoattractant binds to a specific receptor that activates a number of responses including chemotaxis. While much is known about the molecular interactions and signaling pathways that regulate the response to individual cues, little is known about how these pathways process multiple cues to effect migration in the appropriate direction.

The goal of this work is to understand how neutrophils integrate and prioritize multiple chemotactic cues. To this end, we investigated neutrophil migration in response to different chemo-attractants gradients created in microfluidic platforms. By analysis of the migration behavior of the cells in response to single and opposing gradients of chemo-attractants, we have begun to elucidate how neutrophils differentiate between multiple chemoattractant gradients. These results provide insight into a key step during the inflammatory response and should aid in design of novel therapeutic strategies to treat immune-based disorders.