(77c) Neutrophil Migratory Response In Competing Endogenous Chemotactic Gradients

Neutrophils, the most abundant type of white blood cells, play an essential role in the primary stages of the cellular immune response. These cells efficiently sense and migrate up concentration gradients of chemical attractants toward sites of infection and inflammation in a process termed chemotaxis. Such chemoattractants include end-target chemoattractants produced at or proximal to the source of infection, as well as endogenous chemoattractants produced by inflamed host tissues. While much is known about the molecular interactions and signaling pathways that regulate cellular responses to individual cues, little is known about how cells process multiple cues to effect migration in the appropriate direction in vivo.

The aim of this work is to understand how neutrophils integrate and prioritize multiple chemotactic signals to navigate toward pathogens. We investigate neutrophil migration in response to multiple chemoattractant gradients through the generation of precisely controlled microenvironments using microfluidic platforms. By analyzing the migratory response of the cells in response to single and dual gradients of endogenous chemoattractants, we have begun to elucidate how neutrophils respond to multiple chemotactic cues. The peculiar chemotactic behavior of primary neutrophils in competing endogenous gradients suggests the role of directional persistence and cellular memory in guiding cells to their targets. These results provide insight into key mechanisms underlying inflammatory response and should aid in the design of novel immunotherapeutic strategies.