title: Spontaneous neutrophil migration patterns during sepsis after major burns.
abstract: Finely tuned to respond quickly to infections, neutrophils have amazing abilities to migrate fast and efficiently towards sites of infection and inflammation. Although neutrophils ability to migrate is perturbed in patients after major burns, no correlations have yet been demonstrated between altered migration and higher rate of infections and sepsis in these patients when compared to healthy individuals. To probe if such correlations exist, we designed microfluidic devices to quantify the neutrophil migration phenotype with high precision. Inside these devices, moving neutrophils are confined in channels smaller than the neutrophils and forced to make directional decisions at bifurcations and around posts. We employed these devices to quantify neutrophil migration across 18 independent parameters in 74 blood samples from 13 patients with major burns and 3 healthy subjects. Blinded, retrospective analysis of clinical data and neutrophil migration parameters revealed that neutrophils isolated from blood samples collected during sepsis migrate spontaneously inside the microfluidic channels. The spontaneous neutrophil migration is a unique phenotype, typical for patients with major burns during sepsis and often observed one or two days before the diagnosis of sepsis is confirmed. The spontaneous neutrophil migration phenotype is rare in patients with major burns in the absence of sepsis, and is not encountered in healthy individuals. Our findings warrant further studies of neutrophils and their utility for early diagnosing and monitoring sepsis in patients after major burns.
authors.affiliation: Surgery Department, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; BioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Boston, Massachusetts, United States of America; Shriners Hospital for Children, Boston, Massachusetts, United States of America.
authors.forename: Caroline N
authors.initials: CN
authors.lastname: Jones
authors.affiliation: Surgery Department, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Molly
authors.initials: M
authors.lastname: Moore
authors.affiliation: Surgery Department, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; BioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Boston, Massachusetts, United States of America.
authors.forename: Laurie
authors.initials: L
authors.lastname: Dimisko
authors.affiliation: Surgery Department, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Andrew
authors.initials: A
authors.lastname: Alexander
authors.affiliation: Surgery Department, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Shriners Hospital for Children, Boston, Massachusetts, United States of America.
authors.forename: Amir
authors.initials: A
authors.lastname: Ibrahim
authors.affiliation: BioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Boston, Massachusetts, United States of America.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Hassell
authors.affiliation: Shriners Hospital for Children, Boston, Massachusetts, United States of America; Departments of Pediatrics and Medicine, Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: H Shaw
authors.initials: HS
authors.lastname: Warren
authors.affiliation: Surgery Department, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
authors.affiliation: Surgery Department, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Fagan
authors.affiliation: Surgery Department, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; BioMEMS Resource Center, Center for Engineering in Medicine and Surgical Services, Boston, Massachusetts, United States of America; Shriners Hospital for Children, Boston, Massachusetts, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Irimia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002056:Burns / Q000150:complications*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007154:Immune System Diseases / Q000150:complications*; D007960:Leukocyte Disorders / Q000150:complications*; D008297:Male; D046210:Microfluidic Analytical Techniques; D008875:Middle Aged; D010641:Phenotype; D012189:Retrospective Studies; D018805:Sepsis / Q000150:complications* / Q000175:diagnosis / Q000276:immunology*; D055815:Young Adult