Review: Leucocyte–endothelial cell crosstalk at the blood–brain barrier: A prerequisite for successful immune cell entry to the brain
Abstract
J. Greenwood, S. J. Heasman, J. I. Alvarez, A. Prat, R. Lyck and B. Engelhardt (2011) Neuropathology and Applied Neurobiology37, 24–39 Leucocyte–endothelial cell crosstalk at the blood–brain barrier: A prerequisite for successful immune cell entry to the brain Leucocyte migration into the central nervous system is a key stage in the development of multiple sclerosis. While much has been learnt regarding the sequential steps of leucocyte capture, adhesion and migration across the vasculature, the molecular basis of leucocyte extravasation is only just being unravelled. It is now recognized that bidirectional crosstalk between the immune cell and endothelium is an essential element in mediating diapedesis during both normal immune surveillance and under inflammatory conditions. The induction of various signalling networks, through engagement of cell surface molecules such as integrins on the leucocyte and immunoglobulin superfamily cell adhesion molecules on the endothelial cell, play a major role in determining the pattern and route of leucocyte emigration. In this review we discuss the extent of our knowledge regarding leucocyte migration across the blood–brain barrier and in particular the endothelial cell signalling pathways contributing to this process.
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Adhesion occurs via interactions between leukocyte integrins LFA-1 and VLA-4 with endothelial ICAM-1 and VCAM-1, respectively.
“Adhesion occurs via interactions between leukocyte integrins lymphocyte function-associated antigen-1 (LFA-1) and very late antigen-4 (VLA-4) with endothelial ICAM-1 and VCAM-1, respectively (215, 216).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [215]
Paracellular diapedesis is regulated by endothelial VE-cadherin, JAM-A, ESAM, PECAM1, and CD99 and leukocyte LFA-1, PECAM1, and CD99.
“Paracellular diapedesis is regulated by endothelial VE-cadherin, JAM-A, ESAM, PECAM1, and CD99 and leukocyte LFA-1, PECAM1, and CD99 (161, 215, 617) (FIGURE 10) .”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [215]
Additional essential protein interactions for transendothelial diapedesis include endothelial JAM-A, caveolin-1, PECAM1, and CD99 and leukocyte LFA-1, alpha-4-integrin, PECAM1, and CD99.
“Additional essential protein interactions for transendothelial diapedesis include endothelial JAM-A, caveolin-1, PECAM1, and CD99 and leukocyte LFA-1, proteins 𝛂 4-integrin (CD49), PECAM1, and CD99 (165, 215, 655).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [215]
Both leukocytes and the endothelium become activated, causing upregulation of cell surface receptors mediating leukocyte-endothelial adhesion.
“Both leukocytes and the endothelium become activated, causing upregulation of cell surface receptors mediating leukocyte-endothelial adhesion (215, 216, 537).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [215]
In experimental autoimmune encephalomyelitis models, a key pathophysiological event is encephalitogenic leukocyte CNS infiltration across the blood-brain barrier via sequential steps of capture, rolling, activation, adhesion, crawling, and diapedesis in postcapillary venules, capillaries, and mid-capillaries.
“Experimental findings in MS models of chronic and relapsing EAE have shown that a key pathophysiological event is encephalitogenic leukocyte CNSinfiltration across the BBB that occurs via sequential steps of capture, rolling, activation, adhesion, crawling, and diapedesis in postcapillary venules, capillaries, and mid-capillaries (161, 182, 215, 216, 456, 617)”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [215]
Once arrested, leukocytes may polarize and migrate through integrin/CAM-mediated events to enter the perivascular space.
“Once the leukocyte has arrested on the endothelial surface, it may then polarize and migrate through tightly regulated integrin/ CAM-mediated events (eg, VCAM/ICAM) to enter into the perivascular space (Greenwood et al, 2011).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Greenwood et al, 2011
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References 140 · Cited by 240
- Authors
- Greenwood, J., Heasman, S. J., Alvarez, J. I., Prat, A., Lyck, R., & Engelhardt, B.
- Affiliations
- University College London (GB)
- Université de Montréal (CA)
- University of Bern (CH)
- Corresponding author
- Greenwood, J.
- Venue
- Neuropathology and Applied Neurobiology
- Publisher
- Wiley
- Published
- 2011-01-11
- Volume
- 37
- Issue
- 1
- Pages
- 24-39
- ISSN
- 0305-1846 (ISSN-L)
- 1365-2990
- OpenAlex
- W1942368010
- Cited by
- 240
- References
- 140
- Citations by year
- 2026: 11 · 2025: 6 · 2024: 10 · 2023: 9 · 2022: 13 · 2021: 17 · 2020: 13 · 2019: 11 · 2018: 13 · 2017: 14 · 2016: 16 · 2015: 18 · 2014: 30 · 2013: 19 · 2012: 24
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropathology and Applied Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- blood-brain barrier, leukocyte migration, transendothelial migration, multiple sclerosis, integrins, immunoglobulin superfamily cell adhesion molecules, immune surveillance
- MeSH terms
- Animals, Blood-Brain Barrier, Brain, Cell Communication, Cell Movement, Endothelium, Vascular, Humans, Leukocytes, Signal Transduction, Cell Adhesion Molecules, Intercellular Adhesion Molecule-1, Endothelial Cells
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