Neutrophil perfect functioning is essential for our well-being. Without neutrophils, we could only survive a few days the constant assault of bacteria and fungi in our normal environment. A tremendous selective pressure on neutrophils to function perfectly in a large number of conditions made neutrophils one of the most efficient and remarkable cells in terms of migration speed and ability to reach distant targets. However, there are several conditions where neutrophil activity could produce more damage than benefits. While neutrophil activation is protective after minor trauma, hyper-active neutrophils after major injuries have systemic deleterious effects and can effectively damage several organs and tissues, even in the absence of infection. Many conditions like chronic inflammatory diseases, immune reactions post-organ transplantation, or severe forms of asthma can be exacerbated by active neutrophils. Other times, neutrophils become unresponsive, simultaneously with down-regulation of the immune system, leading to, or facilitating septic states. Despite tremendous advances in the understanding of signaling molecules and pathways acting inside neutrophils, our understanding of the changes in neutrophils during disease processes is limited, and consequently, or abilities to modulate the activity of neutrophils in health and disease, restricted to very few options. We believe that advances in understating of neutrophil activity could come not only from molecular biology studies, but also from the development of new tools that would enable the discovery of neutrophil behavior in conditions relevant to in vivo situations. Recently, we demonstrated the surprisingly uniform motility of neutrophils when moving in micro-channels smaller in size than the cell. Using simple networks of channels, we have observed the surprising ability of neutrophils to find the shortest path towards a source of chemoattractant. We will further develop these complex devices to answer questions about the mechanical and chemical requirements for neutrophil decision making inside tissues, in health and disease, regarding the interplay between these in neutrophil biology, and to uncover new therapeutic strategies for controlling inflammation in burn and other critically ill patients.

Public Health Relevance

Neutrophil perfect functioning is essential for our well-being and protection against many infectious agents from our close environment. . However, there are several conditions where neutrophil activity could produce more damage than benefits and new tools are needed to better characterize neutrophils in these conditions. While current methods for studying neutrophils relay exclusively on chemical stimulation of the cells, we have recently shown that the mechanical confinement of the neutrophils in small channels is of utmost importance for neutrophil behavior. To better understand neutrophil alterations of activity following burn injuries, we will apply new microfluidic tools and quantify the responses of neutrophils to combined mechanical and chemical stimuli, in health and disease conditions. This understanding could results in new opportunities for uncovering effective therapeutic strategies for controlling inflammation in burn and other critically ill patients.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Enabling Bioanalytical and Biophysical Technologies Study Section (EBT)
Program Officer
Somers, Scott D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Boneschansker, Leo; Nakayama, Hironao; Eisenga, Michele et al. (2016) Netrin-1 Augments Chemokinesis in CD4+ T Cells In Vitro and Elicits a Proinflammatory Response In Vivo. J Immunol 197:1389-98
Boneschansker, Leo; Inoue, Yoshitaka; Oklu, Rahmi et al. (2016) Capillary plexuses are vulnerable to neutrophil extracellular traps. Integr Biol (Camb) 8:149-55
Norling, Lucy V; Headland, Sarah E; Dalli, Jesmond et al. (2016) Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis. JCI Insight 1:e85922
Skoge, Monica; Wong, Elisabeth; Hamza, Bashar et al. (2016) A Worldwide Competition to Compare the Speed and Chemotactic Accuracy of Neutrophil-Like Cells. PLoS One 11:e0154491
Inoue, Yoshitaka; Yu, Yong-Ming; Kurihara, Tomohiro et al. (2016) Kidney and Liver Injuries After Major Burns in Rats Are Prevented by Resolvin D2. Crit Care Med 44:e241-52
Irimia, Daniel; Ellett, Felix (2016) Big insights from small volumes: deciphering complex leukocyte behaviors using microfluidics. J Leukoc Biol 100:291-304
Bruneau, Sarah; Wedel, Johannes; Fakhouri, Fadi et al. (2016) Translational implications of endothelial cell dysfunction in association with chronic allograft rejection. Pediatr Nephrol 31:41-51
Prentice-Mott, Harrison V; Meroz, Yasmine; Carlson, Andreas et al. (2016) Directional memory arises from long-lived cytoskeletal asymmetries in polarized chemotactic cells. Proc Natl Acad Sci U S A 113:1267-72
Jones, Caroline N; Hoang, Anh N; Martel, Joseph M et al. (2016) Microfluidic assay for precise measurements of mouse, rat, and human neutrophil chemotaxis in whole-blood droplets. J Leukoc Biol 100:241-7
Jones, Caroline N; Dimisko, Laurie; Forrest, Kevin et al. (2016) Human Neutrophils Are Primed by Chemoattractant Gradients for Blocking the Growth of Aspergillus fumigatus. J Infect Dis 213:465-75

Showing the most recent 10 out of 45 publications