TNFα Transport across the Blood–Brain Barrier Is Abolished in Receptor Knockout Mice
Abstract
The presence of transport systems at the blood-brain barrier (BBB) enables some cytokines in blood to reach specific targets in the brain and spinal cord. The "transporters" function in a way different from conventional receptors, in that cytokines are chaperoned from blood to the CNS rather than being degraded in the specialized endothelial cells composing the BBB. Here we present the first study to determine whether the transporter for tumor necrosis factor-alpha (TNFalpha) is identical to its receptors. Three types of TNFalpha receptor knockout mice were used, and the influx of (125)I-TNFalpha from blood to brain and blood to spinal cord was measured. In either p55 or p75 receptor knockout mice, the influx of (125)I-TNFalpha was significantly, but not completely, decreased in spinal cord, whereas the decrease in brain was not statistically significant. This indicates that both receptors are partially involved in the transport of TNFalpha across the BBB but that neither receptor is the sole transporter. By contrast, in double knockout mice lacking both p55 and p75 receptors, the entry of (125)I-TNFalpha into brain and spinal cord was completely abolished. Therefore, both receptors are necessary for transporting TNFalpha across the BBB. The results clearly demonstrate that the transport of TNFalpha across the BBB is a complicated process involving additive or even synergistic activities of both receptors, thus differing from typical ligand-receptor binding and downstream signal transduction.
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Cytokines are transported into the CNS by using saturable transport mechanisms.
“Cytokines are transported into the CNS by using saturable transport mechanisms.”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [99]
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- Authors
- Pan, W., & Kastin, A. J.
- Affiliations
- Tulane University (US)
- Corresponding author
- Pan, Weihong
- ORCID
- Pan, Weihong
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2002-04
- Volume
- 174
- Issue
- 2
- Pages
- 193-200
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2023830686
- Cited by
- 210
- References
- 38
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 7 · 2023: 7 · 2022: 9 · 2021: 14 · 2020: 12 · 2019: 15 · 2018: 9 · 2017: 7 · 2016: 11 · 2015: 11 · 2014: 14 · 2013: 9 · 2012: 11
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (AA12865, R01AA012865)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-54880)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- TNF-α, blood-brain barrier, cytokine transport, TNF receptor p55, TNF receptor 2, receptor knockout mice, spinal cord, brain, endothelial cells, neuroinflammation
- MeSH terms
- Animals, Blood-Brain Barrier, Brain, Iodine Radioisotopes, Spinal Cord, Tumor Necrosis Factor-alpha, Antigens, CD, Receptors, Tumor Necrosis Factor, Mice, Knockout, Protein Transport, Receptors, Tumor Necrosis Factor, Type I, Receptors, Tumor Necrosis Factor, Type II, Mice
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