Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2011 Feb;1812(2):220-30.
doi: 10.1016/j.bbadis.2010.07.019. Epub 2010 Aug 6.

The blood-brain barrier, chemokines and multiple sclerosis

David W Holman  1 , Robyn S Klein, Richard M Ransohoff
Affiliations
Review

The blood-brain barrier, chemokines and multiple sclerosis

David W Holman et al. Biochim Biophys Acta. 2011 Feb.

Abstract

The infiltration of leukocytes into the central nervous system (CNS) is an essential step in the neuropathogenesis of multiple sclerosis (MS). Leukocyte extravasation from the bloodstream is a multistep process that depends on several factors including fluid dynamics within the vasculature and molecular interactions between circulating leukocytes and the vascular endothelium. An important step in this cascade is the presence of chemokines on the vascular endothelial cell surface. Chemokines displayed along the endothelial lumen bind chemokine receptors on circulating leukocytes, initiating intracellular signaling that culminates in integrin activation, leukocyte arrest, and extravasation. The presence of chemokines at the endothelial lumen can help guide the movement of leukocytes through peripheral tissues during normal immune surveillance, host defense or inflammation. The expression and display of homeostatic or inflammatory chemokines therefore critically determine which leukocyte subsets extravasate and enter the peripheral tissues. Within the CNS, however, infiltrating leukocytes that cross the endothelium face additional boundaries to parenchymal entry, including the abluminal presence of localizing cues that prevent egress from perivascular spaces. This review focuses on the differential display of chemokines along endothelial surfaces and how they impact leukocyte extravasation into parenchymal tissues, especially within the CNS. In particular, the display of chemokines by endothelial cells of the blood brain barrier may be altered during CNS autoimmune disease, promoting leukocyte entry into this immunologically distinct site. Recent advances in microscopic techniques, including two-photon and intravital imaging have provided new insights into the mechanisms of chemokine-mediated capture of leukocytes within the CNS.

PubMed Disclaimer

Figures

Figure 1
Figure 1. CXCL12 receptors regulate leukocyte access to CNS parenchyma
Within the CNS, CXCL12 expression is localized to the microvasculature along the parenchymal facing surface of endothelial cells under physiological conditions. This abluminal expression pattern of CXCL12 functions to retain CXCR4 and CXCR7 expressing leukocytes within the perivascular space, preventing their access to the brain parenchyma proper. In neuroinflammatory conditions such as the animal model EAE and in human MS, CXCL12 polarization is lost and CXCL12 translocates towards the vessel lumen. CXCR4 and CXCR7 expressing leukocytes lose their localizing cues and can infiltrate further into the parenchymal tissues subsequently inducing demyelination. Further, display of CXCL12 along the lumenal endothelial surface may provide further signaling to circulating CXCR4/CXCR7+ T-cells leading to increased T-cell recruitment and transendothelial migration.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ransohoff RM, Kivisakk P, Kidd G. Three or more routes for leukocyte migration into the central nervous system. Nat Rev Immunol. 2003;3:569–81. - PubMed
    1. Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci. 2006;7:41–53. - PubMed
    1. Johanson CE, Duncan JA, 3rd, Klinge PM, Brinker T, Stopa EG, Silverberg GD. Multiplicity of cerebrospinal fluid functions: New challenges in health and disease. Cerebrospinal Fluid Res. 2008;5:10. - PMC - PubMed
    1. Ge S, Song L, Pachter JS. Where is the blood-brain barrier... really? J Neurosci Res. 2005;79:421–7. - PubMed
    1. Chi JT, Chang HY, Haraldsen G, Jahnsen FL, Troyanskaya OG, Chang DS, Wang Z, Rockson SG, van de Rijn M, Botstein D, Brown PO. Endothelial cell diversity revealed by global expression profiling. Proc Natl Acad Sci U S A. 2003;100:10623–8. - PMC - PubMed

MeSH terms