title: Burn injury reduces neutrophil directional migration speed in microfluidic devices.
abstract: Thermal injury triggers a fulminant inflammatory cascade that heralds shock, end-organ failure, and ultimately sepsis and death. Emerging evidence points to a critical role for the innate immune system, and several studies had documented concurrent impairment in neutrophil chemotaxis with these post-burn inflammatory changes. While a few studies suggest that a link between neutrophil motility and patient mortality might exist, so far, cumbersome assays have prohibited exploration of the prognostic and diagnostic significance of chemotaxis after burn injury. To address this need, we developed a microfluidic device that is simple to operate and allows for precise and robust measurements of chemotaxis speed and persistence characteristics at single-cell resolution. Using this assay, we established a reference set of migration speed values for neutrophils from healthy subjects. Comparisons with samples from burn patients revealed impaired directional migration speed starting as early as 24 hours after burn injury, reaching a minimum at 72-120 hours, correlated to the size of the burn injury and potentially serving as an early indicator for concurrent infections. Further characterization of neutrophil chemotaxis using this new assay may have important diagnostic implications not only for burn patients but also for patients afflicted by other diseases that compromise neutrophil functions.
authors.affiliation: Surgery Department, Massachusetts General Hospital, Shriners Hospital for Children, and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Butler
authors.forename: Vijayakrishnan
authors.initials: V
authors.lastname: Ambravaneswaran
authors.forename: Nitin
authors.initials: N
authors.lastname: Agrawal
authors.forename: Maryelizabeth
authors.initials: M
authors.lastname: Bilodeau
authors.forename: Mehmet
authors.initials: M
authors.lastname: Toner
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
authors.forename: Shawn
authors.initials: S
authors.lastname: Fagan
authors.forename: Daniel
authors.initials: D
authors.lastname: Irimia
mesh_terms: D000328:Adult; D000368:Aged; D002056:Burns / Q000276:immunology* / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology*; D055815:Young Adult