Burn Injury Reduces Neutrophil Directional Migration Speed in Microfluidic Devices

• Published in: PloS one Vol. 5; no. 7; p. e11921
• Main Authors: Butler, Kathryn L., Ambravaneswaran, Vijayakrishnan, Agrawal, Nitin, Bilodeau, Maryelizabeth, Toner, Mehmet, Tompkins, Ronald G., Fagan, Shawn, Irimia, Daniel
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.07.2010; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Assaying; Bacterial infections; Biotechnology/Bioengineering; Blood; Blood transfusions; Burn patients; Burns; Burns - immunology; Burns - pathology; Cell culture; Cell Movement - physiology; Chemotaxis; Clinical outcomes; Critical Care and Emergency Medicine/Trauma; Diagnostic systems; Engineering; Female; Granulocytes; Health aspects; Hospitals; Humans; Hydrogels; Immune system; Immunology/Innate Immunity; Infection; Infections; Inflammation; Injuries; Injury prevention; Innate immunity; Leukocyte migration; Leukocytes (neutrophilic); Male; Medical research; Medical schools; Medicine; Microfluidic Analytical Techniques - methods; Microfluidics; Middle Aged; Mortality; Neutrophils; Neutrophils - cytology; Patients; Sepsis; Studies; Surgery; Thermal injury; Trauma; Young Adult; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0011921

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.