Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Pharmacology and Experimental Therapeutics
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleNeuropharmacology

Rapid Transport of CCL11 across the Blood-Brain Barrier: Regional Variation and Importance of Blood Cells

Michelle A. Erickson, Yoichi Morofuji, Joshua B. Owen and William A. Banks
Journal of Pharmacology and Experimental Therapeutics June 2014, 349 (3) 497-507; DOI: https://doi.org/10.1124/jpet.114.213074
Michelle A. Erickson
University of Pennsylvania, Department of Pathology, School of Dental Medicine, Philadelphia, Pennsylvania (M.A.E.); Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington (M.A.E., Y.M., J.B.O., W.A.B.); Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington School of Medicine, Seattle, Washington (M.A.E., Y.M., J.B.O., W.A.B.); Department of Chemistry, University of Kentucky, Lexington, Kentucky (J.B.O.); and Department of Neurosurgery, University of Nagasaki, Nagasaki, Japan (Y.M.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yoichi Morofuji
University of Pennsylvania, Department of Pathology, School of Dental Medicine, Philadelphia, Pennsylvania (M.A.E.); Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington (M.A.E., Y.M., J.B.O., W.A.B.); Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington School of Medicine, Seattle, Washington (M.A.E., Y.M., J.B.O., W.A.B.); Department of Chemistry, University of Kentucky, Lexington, Kentucky (J.B.O.); and Department of Neurosurgery, University of Nagasaki, Nagasaki, Japan (Y.M.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joshua B. Owen
University of Pennsylvania, Department of Pathology, School of Dental Medicine, Philadelphia, Pennsylvania (M.A.E.); Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington (M.A.E., Y.M., J.B.O., W.A.B.); Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington School of Medicine, Seattle, Washington (M.A.E., Y.M., J.B.O., W.A.B.); Department of Chemistry, University of Kentucky, Lexington, Kentucky (J.B.O.); and Department of Neurosurgery, University of Nagasaki, Nagasaki, Japan (Y.M.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
William A. Banks
University of Pennsylvania, Department of Pathology, School of Dental Medicine, Philadelphia, Pennsylvania (M.A.E.); Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington (M.A.E., Y.M., J.B.O., W.A.B.); Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington School of Medicine, Seattle, Washington (M.A.E., Y.M., J.B.O., W.A.B.); Department of Chemistry, University of Kentucky, Lexington, Kentucky (J.B.O.); and Department of Neurosurgery, University of Nagasaki, Nagasaki, Japan (Y.M.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Increased blood levels of the eotaxin chemokine C-C motif ligand 11 (CCL11) in aging were recently shown to negatively regulate adult hippocampal neurogenesis. How circulating CCL11 could affect the central nervous system (CNS) is not clear, but one possibility is that it can cross the blood-brain barrier (BBB). Here, we show that CCL11 undergoes bidirectional transport across the BBB. Transport of CCL11 from blood into whole brain (influx) showed biphasic kinetics, with a slow phase preceding a rapid phase of uptake. We found that the slow phase was explained by binding of CCL11 to cellular components in blood, whereas the rapid uptake phase was mediated by direct interactions with the BBB. CCL11, even at high doses, did not cause BBB disruption. All brain regions except striatum showed a delayed rapid-uptake phase. Striatum had only an early rapid-uptake phase, which was the fastest of any brain region. We also observed a slow but saturable transport system for CCL11 from brain to blood. C-C motif ligand 3 (CCR3), an important receptor for CCL11, did not facilitate CCL11 transport across the BBB, although high concentrations of a CCR3 inhibitor increased brain uptake without causing BBB disruption. Our results indicate that CCL11 in the circulation can access many regions of the brain outside of the neurogenic niche via transport across the BBB. This suggests that blood-borne CCL11 may have important physiologic functions in the CNS and implicates the BBB as an important regulator of physiologic versus pathologic effects of this chemokine.

Footnotes

    • Received January 12, 2014.
    • Accepted March 3, 2014.
  • This work was supported by the National Institutes of Health National Institute on Aging [Grant R01-AG029839]; and National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant R01-NS051334].

  • dx.doi.org/10.1124/jpet.114.213074.

  • U.S. Government work not protected by U.S. copyright
View Full Text

JPET articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 349 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 349, Issue 3
1 Jun 2014
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Rapid Transport of CCL11 across the Blood-Brain Barrier: Regional Variation and Importance of Blood Cells
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleNeuropharmacology

CCL11 Transport across the Blood-Brain Barrier

Michelle A. Erickson, Yoichi Morofuji, Joshua B. Owen and William A. Banks
Journal of Pharmacology and Experimental Therapeutics June 1, 2014, 349 (3) 497-507; DOI: https://doi.org/10.1124/jpet.114.213074

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleNeuropharmacology

CCL11 Transport across the Blood-Brain Barrier

Michelle A. Erickson, Yoichi Morofuji, Joshua B. Owen and William A. Banks
Journal of Pharmacology and Experimental Therapeutics June 1, 2014, 349 (3) 497-507; DOI: https://doi.org/10.1124/jpet.114.213074
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Glycine receptor modulation using monoclonal antibodies
  • Iclepertin (BI 425809) in Schizophrenia-Related Models
  • D1 Agonist Versus Methylphenidate on PFC Working Memory
Show more Neuropharmacology

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About JPET
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics