PUBLICATION

Factor Associated with Neutral Sphingomyelinase Activity Mediates Navigational Capacity of Leukocytes Responding to Wounds and Infection: Live Imaging Studies in Zebrafish Larvae

Authors
Boecke, A., Sieger, D., Neacsu, C.D., Kashkar, H., and Krönke, M.
ID
ZDB-PUB-120718-43
Date
2012
Source
Journal of immunology (Baltimore, Md. : 1950)   189(4): 1559-1566 (Journal)
Registered Authors
Sieger, Dirk
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Bacterial Infections/immunology*
  • Bacterial Infections/metabolism
  • Chemotaxis, Leukocyte
  • In Situ Hybridization
  • Intracellular Signaling Peptides and Proteins/immunology
  • Intracellular Signaling Peptides and Proteins/metabolism*
  • Larva
  • Leukocytes/cytology
  • Leukocytes/immunology*
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sphingomyelin Phosphodiesterase/immunology
  • Sphingomyelin Phosphodiesterase/metabolism*
  • Wound Healing/physiology*
  • Zebrafish
PubMed
22802420 Full text @ J. Immunol.
Abstract

Factor associated with neutral sphingomyelinase activity (FAN) is an adaptor protein that specifically binds to the p55 receptor for TNF (TNF-RI). Our previous investigations demonstrated that FAN plays a role in TNF-induced actin reorganization by connecting the plasma membrane with actin cytoskeleton, suggesting that FAN may impact on cellular motility in response to TNF and in the context of immune inflammatory conditions. In this study, we used the translucent zebrafish larvae for in vivo analysis of leukocyte migration after morpholino knockdown of FAN. FAN-deficient zebrafish leukocytes were impaired in their migration toward tail fin wounds, leading to a reduced number of cells reaching the wound. Furthermore, FAN-deficient leukocytes show an impaired response to bacterial infections, suggesting that FAN is generally required for the directed chemotactic response of immune cells independent of the nature of the stimulus. Cell-tracking analysis up to 3 h after injury revealed that the reduced number of leukocytes is not due to a reduction in random motility or speed of movement. Leukocytes from FAN-deficient embryos protrude pseudopodia in all directions instead of having one clear leading edge. Our results suggest that FAN-deficient leukocytes exhibit an impaired navigational capacity, leading to a disrupted chemotactic response.

Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes