Rapid Transport of CCL11 across the Blood-Brain Barrier: Regional Variation and Importance of Blood Cells
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CCL11 efficiently crosses the blood brain barrier, has been implicated in neuroinflammatory disorders and SARS-CoV-2 cognitive impairment, and impairs neurogenesis.
“CCL11 efficiently crosses the blood brain barrier56, has been implicated in neuroinflammatory disorders and SARS-CoV-2 (COVID-19) cognitive impairment57,58, and impairs neurogenesis54,58,59.”
From Senescent-like microglia limit remyelination through the senescence associated secretory phenotype (2025) · cites this paper as [56]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A specialized vascular niche for adult neural stem cells
Tavazoie, M., Van der Veken, L., Silva-Vargas, V., Louissaint, M., Colonna, L., Zaidi, B., Garcia-Verdugo, J. M., & Doetsch, F. (2008) · Cell stem cell · doi:10.1016/j.stem.2008.07.025 · Cited by 1,033 · see citing works
Blood-brain barrier transport of cytokines: a mechanism for neuropathology
Banks, W. (2005) · Current Pharmaceutical Design · doi:10.2174/1381612053381684 · Cited by 534 · see citing works
Self-citationInflammatory Proteins in Plasma Are Associated with Severity of Alzheimer’s Disease
Leung, R., Proitsi, P., Simmons, A., Lunnon, K., Güntert, A., Kronenberg, D., Pritchard, M., Tsolaki, M., Mecocci, P., Kloszewska, I., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064971 · Cited by 160 · see citing works
Peripheral Chemokine Levels in Women with Recurrent Major Depression with Suicidal Ideation
Grassi-Oliveira, R., Brieztke, E., Teixeira, A., Pezzi, J. C., Zanini, M., Lopes, R. P., & Bauer, M. E. (2012) · Revista Brasileira de Psiquiatria · doi:10.1590/s1516-44462012000100013 · Cited by 91 · cited 5× · see citing works
“, 2006), psychiatric disorders (Teixeira et al., 2008; Grassi-Oliveira et al., 2012), and cannabis use (Fernandez-Egea et al.”
BackgroundInfluential
Flagged first, then by citations
Research works printed but not linked: 1
- Jorm AF (2000) Is depression a risk factor for dementia or cognitive decline? A review. Gerontology 46:219-227.
Cited by
Sorted by citations
Minter, M. R., Zhang, C., Leone, V., Ringus, D. L., Zhang, X., Oyler-Castrillo, P., Musch, M. W., Liao, F., Ward, J. F., Holtzman, D. M., et al. (2016) · Scientific Reports · doi:10.1038/srep30028 · Cited by 655 · see citing works
Minter, M. R., Hinterleitner, R., Meisel, M., Zhang, C., Leone, V., Zhang, X., Oyler-Castrillo, P., Zhang, X., Musch, M. W., Shen, X., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-11047-w · Cited by 292 · see citing works
The blood-brain barrier in neuroimmunology: Tales of separation and assimilation
Banks, W. A. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2014.08.007 · Cited by 292 · see citing works
Self-citationBlood-to-brain communication in aging and rejuvenation
Bieri, G., Schroer, A. B., & Villeda, S. A. (2023) · Nature Neuroscience · doi:10.1038/s41593-022-01238-8 · Cited by 156 · see citing works
Young bone marrow transplantation preserves learning and memory in old mice
Das, M. M., Godoy, M., Chen, S., Moser, V. A., Avalos, P., Roxas, K. M., Dang, I., Yáñez, A., Zhang, W., Bresee, C., et al. (2019) · Communications Biology · doi:10.1038/s42003-019-0298-5 · Cited by 98 · see citing works
Senescent-like microglia limit remyelination through the senescence associated secretory phenotype
Gross, P. S., Durán-Laforet, V., Ho, L. T., Melchor, G. S., Zia, S., Manavi, Z., Barclay, W. E., Lee, S. H., Shults, N., Selva, S., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-57632-w · Cited by 62 · see citing works
“Recently, it was also shown to interact with the central nervous system inmultipleways:CCL11ef fi cientlycrossesthebloodbrainbarrier 56 ,has been implicated in neuroin fl ammatory disorders and SARS-CoV-2 (COVID-19) cognitive impairment 57,58 , and impairs neurogenesis 54,58,59 .”
Tashiro, R., Ozaki, D., Bautista-Garrido, J., Sun, G., Obertas, L., Mobley, A. S., Kim, G. S., Aronowski, J., & Jung, J. E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065187 · Cited by 15 · see citing works
Vascular Senescence: A Potential Bridge Between Physiological Aging and Neurogenic Decline
Rojas-Vázquez, S., Blasco-Chamarro, L., López-Fabuel, I., Martínez-Máñez, R., & Fariñas, I. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.666881 · Cited by 15 · see citing works
- Authors
- Erickson, M. A., Morofuji, Y., Owen, J. B., & Banks, W. A.
- Affiliations
- University of Nagasaki (JP)
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 349
- Issue
- 3
- Pages
- 497-507
- ISSN
- 0022-3565 (ISSN-L)
- PMC
- PMC4019322
- OpenAlex
- W2168315986
- Cited by
- 110
- References
- 4
- Citations by year
- 2026: 5 · 2025: 19 · 2024: 10 · 2023: 7 · 2022: 9 · 2021: 10 · 2020: 8 · 2019: 8 · 2018: 8 · 2017: 10 · 2016: 11 · 2015: 4 · 2014: 1
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AG029839)
- National Institute on Aging (R01AG029839)
- National Institute of Neurological Disorders and Stroke (R01NS051334)
- National Institute of Environmental Health Sciences (T32ES019851, P30ES013508)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- eotaxin, blood-brain barrier, bidirectional transport, striatum, CCR3, hippocampal neurogenesis, aging, blood-brain barrier disruption
- MeSH terms
- Animals, Biological Transport, Blood-Brain Barrier, Brain, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Injections, Intravenous, Iodine Radioisotopes, Male, Regression Analysis, Tissue Distribution, Endothelial Cells, Mice, Chemokine CCL11, Primary Cell Culture
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
