title: Capillary plexuses are vulnerable to neutrophil extracellular traps.
abstract: Capillary plexuses are commonly regarded as reliable networks for blood flow and robust oxygen delivery to hypoxia sensitive tissues. They have high levels of redundancy to assure adequate blood supply when one or more of the capillaries in the network are blocked by a clot. However, despite having extensive capillary plexuses, many vital organs are often subject to secondary organ injury in patients with severe inflammation. Recent studies have suggested that neutrophils play a role in this pathology, even though their precise contribution remains elusive. Here we investigate the effect of chromatin fibres released from overly-activated neutrophils (neutrophil extracellular traps, NETs) on the flow of blood through microfluidic networks of channels replicating geometrical features of capillary plexuses. In an in vitro setting, we show that NETs can decouple the traffic of red blood cells from that of plasma in microfluidic networks. The effect is astonishingly disproportionate, with NETs from less than 200 neutrophils resulting in more than half of a 0.6 mm(2) microfluidic network to become void of red blood cell traffic. Importantly, the NETs are able to perturb the blood flow in capillary networks despite the presence of anti-coagulants. If verified to occur in vivo, this finding could represent a novel mechanism for tissue hypoxia and secondary organ injury during severe inflammation in patients already receiving antithrombotic and anticoagulant therapies.
authors.affiliation: BioMEMS Resource Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Shriners Burns Hospital, Boston, MA 02129, USA. dirimia@hms.harvard.edu.
authors.forename: Leo
authors.initials: L
authors.lastname: Boneschansker
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Inoue
authors.forename: Rahmi
authors.initials: R
authors.lastname: Oklu
authors.forename: Daniel
authors.initials: D
authors.lastname: Irimia
mesh_terms: D000328:Adult; D002196:Capillaries / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry; D004396:Coloring Agents / Q000737:chemistry; D003851:Deoxyribonucleases / Q000737:chemistry; D004912:Erythrocytes / Q000166:cytology; D065206:Extracellular Traps; D006801:Humans; D000860:Hypoxia; D007249:Inflammation; D056656:Lab-On-A-Chip Devices; D044085:Microfluidics / Q000379:methods; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry; D013927:Thrombosis / Q000378:metabolism; D055815:Young Adult
chemical_list: D002843:Chromatin; D004396:Coloring Agents; D003851:Deoxyribonucleases; D010100:Oxygen