Neutrophil Chemotaxis in Multiple Chemoattractant Gradients Using Microfluidic Platforms

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 intermediary (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 goal of this work is to understand how neutrophils integrate and prioritize multiple chemotactic signals to navigate toward pathogens. To this end, we investigated neutrophil migration in response to multiple chemoattractant gradients through the generation of precisely controlled microenvironments using microfluidics. By analyzing the migration behavior of the cells in response to single and dual gradients of chemoattractants (IL8, LTB4 and fMLP), we have begun to elucidate how neutrophils respond to complex overlapping chemotactic cues. The chemotactic behavior of primary neutrophils suggests the role of directional persistence and cellular memory in guiding cells to their targets. These results provide insight into a key component of the inflammatory response and should aid in the design of novel therapeutic strategies to treat certain immune-based health disorders.