PUBLICATION

Intravital correlated microscopy reveals differential macrophage and microglial dynamics during resolution of neuroinflammation

Authors
van Ham, T.J., Brady, C.A., Kalicharan, R.D., Oosterhof, N., Kuipers, J., Veenstra-Algra, A., Sjollema, K.A., Peterson, R.T., Kampinga, H.H., Giepmans, B.N.
ID
ZDB-PUB-140629-3
Date
2014
Source
Disease models & mechanisms   7: 857-869 (Journal)
Registered Authors
Peterson, Randall, van Ham, Tjakko
Keywords
Brain, Intravital microscopy, Leukocytes, Microglia, Neurodegeneration, Zebrafish
MeSH Terms
  • Membrane Glycoproteins/metabolism
  • Larva
  • Brain/pathology*
  • Brain/ultrastructure
  • Animals
  • Astrocytes/pathology
  • Microfilament Proteins/metabolism
  • Phagocytosis
  • Zebrafish
  • Cell Count
  • Time Factors
  • Green Fluorescent Proteins/metabolism
  • Neurons/pathology
  • Cell Death
  • Macrophages/pathology*
  • Microscopy/methods*
  • Neutrophils/pathology
  • Apolipoproteins E/metabolism
  • Microglia/pathology*
  • Microglia/ultrastructure
  • Inflammation/pathology*
  • Phagocytes/pathology
  • Phagocytes/ultrastructure
(all 23)
PubMed
24973753 Full text @ Dis. Model. Mech.
Abstract
Many brain diseases involve activation of resident and peripheral immune cells to clear damaged and dying neurons. Which immune cells respond in what way to cues related to brain disease, however, remains poorly understood. To elucidate these in vivo immunological events in response to brain cell death we used genetically targeted cell ablation in zebrafish. Using intravital microscopy and large-scale electron microscopy, we defined the kinetics and nature of immune responses immediately following injury. Initially, clearance of dead cells occurs by mononuclear phagocytes, including resident microglia and macrophages of peripheral origin, whereas amoeboid microglia are exclusively involved at a later stage. Granulocytes, on the other hand, do not migrate towards the injury. Remarkably, following clearance, phagocyte numbers decrease, partly by phagocyte cell death and subsequent engulfment of phagocyte corpses by microglia. Here, we identify differential temporal involvement of microglia and peripheral macrophages in clearance of dead cells in the brain, revealing the chronological sequence of events in neuroinflammatory resolution. Remarkably, recruited phagocytes undergo cell death and are engulfed by microglia. Because adult zebrafish treated at the larval stage lack signs of pathology, it is likely that this mode of resolving immune responses in brain contributes to full tissue recovery. Therefore, these findings suggest that control of such immune cell behavior could benefit recovery from neuronal damage.
Genes / Markers
Figures
Figure Gallery (8 images)
Show all Figures
Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
c264TgTransgenic Insertion
    gl22TgTransgenic Insertion
      i114TgTransgenic Insertion
        zdf11TgTransgenic Insertion
          zf147TgTransgenic Insertion
            zf279EtTransgenic Insertion
              1 - 6 of 6
              Show
              Human Disease / Model
              No data available
              Sequence Targeting Reagents
              No data available
              Fish
              Fish
              c264Tg
              gl22Tg
              i114Tg
              zdf11Tg
              zf147Tg
              zf279Et
              1 - 6 of 6
              Show
              Antibodies
              Name Type Antigen Genes Isotypes Host Organism
              Ab2-lcp1polyclonalRabbit
              1 - 1 of 1
              Show
              Orthology
              No data available
              Engineered Foreign Genes
              Marker Marker Type Name
              EGFPEFGEGFP
              GFPEFGGFP
              KALTA4EFGKALTA4
              mCherryEFGmCherry
              NTREFGNTR
              1 - 5 of 5
              Show
              Mapping
              No data available
              Your Input Welcome
              We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
              Citation
              van Ham, T.J., Brady, C.A., Kalicharan, R.D., Oosterhof, N., Kuipers, J., Veenstra-Algra, A., Sjollema, K.A., Peterson, R.T., Kampinga, H.H., Giepmans, B.N. (2014) Intravital correlated microscopy reveals differential macrophage and microglial dynamics during resolution of neuroinflammation. Disease models & mechanisms. 7:857-869.