title: Exploring inflammatory disease drug effects on neutrophil function.
abstract: Neutrophils are critical inflammatory cells; thus, it is important to characterize the effects of drugs on neutrophil function in the context of inflammatory diseases. Herein, chemically guided neutrophil migration, known as chemotaxis, is studied in the context of drug treatment at the single cell level using a microfluidic platform, complemented by cell viability assays and calcium imaging. Three representative drugs known to inhibit surface receptor expression, signaling enzyme activity, and the elevation of intracellular Ca(2+) levels, each playing a significant role in neutrophil chemotactic pathways, are used to examine the in vitro drug effects on cellular behaviors. The microfluidic device establishes a stable concentration gradient of chemokines across a cell culture chamber so that neutrophil migration can be monitored under various drug-exposure conditions. Different time- and concentration-dependent regulatory effects were observed by comparing the motility, polarization, and effectiveness of neutrophil chemotaxis in response to the three drugs. Viability assays revealed distinct drug capabilities in reducing neutrophil viability while calcium imaging clarified the role of Ca(2+) in the neutrophil chemotaxis. This study provides mechanistic insight into the drug effects on neutrophil function, facilitating comparison of current and potential pharmaceutical approaches.
authors.affiliation: Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, USA. chaynes@umn.edu.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wu
authors.forename: Donghyuk
authors.initials: D
authors.lastname: Kim
authors.forename: Ashlyn T
authors.initials: AT
authors.lastname: Young
authors.forename: Christy L
authors.initials: CL
authors.lastname: Haynes
mesh_terms: D002118:Calcium / Q000032:analysis; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004867:Equipment Design; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D061848:Optical Imaging; D059010:Single-Cell Analysis / Q000295:instrumentation*
chemical_list: D002118:Calcium