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Extravascular CX3CR1+ Cells Extend Intravascular Dendritic Processes into Intact Central Nervous System Vessel Lumen

Published online by Cambridge University Press:  03 May 2013

Deborah S. Barkauskas ,
Teresa A. Evans ,
Jay Myers ,
Agne Petrosiute ,
Jerry Silver  and
Alex Y. Huang
Deborah S. Barkauskas
Affiliation:
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
Teresa A. Evans
Affiliation:
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
Jay Myers
Affiliation:
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
Agne Petrosiute
Affiliation:
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
Jerry Silver
Affiliation:
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
Alex Y. Huang*
Affiliation:
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
*
*Corresponding author. E-mail: alex.y.huang@case.edu
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Abstract

Within the central nervous system (CNS), antigen-presenting cells (APCs) play a critical role in orchestrating inflammatory responses where they present CNS-derived antigens to immune cells that are recruited from the circulation to the cerebrospinal fluid, parenchyma, and perivascular space. Available data indicate that APCs do so indirectly from outside of CNS vessels without direct access to luminal contents. Here, we applied high-resolution, dynamic intravital two-photon laser scanning microscopy to directly visualize extravascular CX3CR1+ APC behavior deep within undisrupted CNS tissues in two distinct anatomical sites under three different inflammatory stimuli. Surprisingly, we observed that CNS-resident APCs dynamically extend their cellular processes across an intact vessel wall into the vascular lumen with preservation of vessel integrity. While only a small number of APCs displayed intravascular extensions in intact, noninflamed vessels in the brain and the spinal cord, the frequency of projections increased over days in an experimental autoimmune encephalomyelitis model, whereas the number of projections remained stable compared to baseline days after tissue injury such as CNS tumor infiltration and aseptic spinal cord trauma. Our observation of this unique behavior by parenchyma CX3CR1+ cells in the CNS argues for further exploration into their functional role in antigen sampling and immune cell recruitment.

Keywords

two-photon microscopyintravitalantigen-presenting cellsblood-brain barriercentral nervous systemmicrogliaspinal cord injuryEAECNS vessels
Type
Omaha Imaging Symposium
Information
Microscopy and Microanalysis , Volume 19 , Issue 4 , August 2013 , pp. 778 - 790
Copyright
Copyright © Microscopy Society of America 2013 

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Footnotes

†

These authors contributed equally to this work.

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