PUBLICATION

Pioneer neutrophils release chromatin within in vivo swarms

Authors
Isles, H.M., Loynes, C.A., Alasmari, S., Kon, F.C., Henry, K.M., Kadochnikova, A., Hales, J., Muir, C.F., Keightley, M.C., Kadirkamanathan, V., Hamilton, N., Lieschke, G.J., Renshaw, S.A., Elks, P.M.
ID
ZDB-PUB-210723-4
Date
2021
Source
eLIFE   10: (Journal)
Registered Authors
Alasmari, Sultan, Elks, Philip, Henry, Katherine, Keightley, M. Cristina, Lieschke, Graham J., Loynes, Catherine, Renshaw, Steve A.
Keywords
NETs, immunology, inflammation, neutrophil, neutrophil swarming, zebrafish
MeSH Terms
  • Animals
  • Cell Aggregation/physiology
  • Chromatin/metabolism*
  • Extracellular Traps/metabolism*
  • Leukocyte Elastase/metabolism
  • Neutrophils/immunology*
  • Neutrophils/pathology
  • Peroxidase/metabolism
  • Wounds and Injuries/immunology
  • Wounds and Injuries/pathology*
  • Zebrafish
PubMed
34292151 Full text @ Elife
Abstract
Neutrophils are rapidly recruited to inflammatory sites where their coordinated migration forms clusters, a process termed neutrophil swarming. The factors that modulate early stages of neutrophil swarming are not fully understood, requiring the development of new in vivo models. Using transgenic zebrafish larvae to study endogenous neutrophil migration in a tissue damage model, we demonstrate that neutrophil swarming is a conserved process in zebrafish immunity, sharing essential features with mammalian systems. We show that neutrophil swarms initially develop around an individual pioneer neutrophil. We observed the violent release of extracellular cytoplasmic and nuclear fragments by the pioneer and early swarming neutrophils. By combining in vitro and in vivo approaches to study essential components of neutrophil extracellular traps (NETs), we provide in-depth characterisation and high-resolution imaging of the composition and morphology of these release events. Using a photoconversion approach to track neutrophils within developing swarms, we identify that the fate of swarm-initiating pioneer neutrophils involves extracellular chromatin release and that the key NET components gasdermin, neutrophil elastase, and myeloperoxidase are required for the swarming process. Together our findings demonstrate that release of cellular components by pioneer neutrophils is an initial step in neutrophil swarming at sites of tissue injury.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping