Cited by 110Cell Adhesion Molecules ResearchBarrier Structure and Function StudiesNeuroinflammation and Neurodegeneration Mechanisms

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Brain endothelium lack one of two pathways of P-selectin-mediated neutrophil adhesion

Barkalow, FJ, Goodman, MJ, Gerritsen, ME, Mayadas, TN·1996·Blood

DOI 10.1182/blood.v88.12.4585.bloodjournal88124585

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Abstract

P-selectin, an endothelial leukocyte adhesion receptor, is rapidly translocated to the cell surface upon release from storage granules called Weibel-Palade bodies and is also transcriptionally upregulated upon cytokine stimulation of endothelial cells (ECs). These two pathways of surface expression are coincident with the rapid and cytokine-inducible pathway of neutrophil adhesion to ECs. Constitutive P-selectin expression is largely absent in cultured murine brain microvascular EC (BMEC) monolayers, but interleukin-1beta and tumor necrosis factor-alpha stimulation for 4 hours leads to dramatic P-selectin upregulation. The functional relevance of differential P-selectin expression in these cells was examined by studying BMECs derived from wild-type mice and P-selectin-deficient mice. We show that P-selectin deficiency does not affect Weibel-Palade body formation or their release in response to short-acting agonists. However, in the absence of P-selectin, the brain endothelium is unable to support neutrophil adhesion after stimulation with these agonists, which may contribute to the immune privilege status of the brain. We show that P- selectin does play a major role in supporting neutrophil adhesion in the cytokine-induced pathway in BMECs in the context of other cytokine- inducible endothelial-leukocyte adhesion receptors, E-selectin, ICAM-1, and VCAM-1.

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Authors: Barkalow, F., Goodman, M., Gerritsen, M., & Mayadas, T.
Affiliations: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Brigham and Women's Hospital (US)
Venue: Blood
Publisher: American Society of Hematology
Published: 1996-12-15
Volume: 88
Issue: 12
Pages: 4585-4593
ISSN: 0006-4971 (ISSN-L)
1528-0020
DOI: 10.1182/blood.v88.12.4585.bloodjournal88124585
OpenAlex: W2338797839
Cited by: 110
References: 42
Citations by year: 2026: 3 · 2025: 1 · 2024: 2 · 2022: 6 · 2021: 4 · 2020: 5 · 2019: 1 · 2018: 5 · 2017: 4 · 2016: 2 · 2015: 5 · 2014: 3 · 2013: 3 · 2012: 5
FWCI: 1.80
Type: journal article
Language: en
Open access: closed
Locations: Blood (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ns033296-02)
National Heart, Lung, and Blood Institute (T32HL007627, 5T32HL07627-10)
National Institute of Neurological Disorders and Stroke (R01-NS33296)
Topics: Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: P-selectin, neutrophil adhesion, brain microvascular endothelial cells, Weibel-Palade bodies, IL-1β, TNF-α, immune privilege, E-selectin, ICAM-1, VCAM-1, leukocyte adhesion molecules
MeSH terms: Animals, Brain, Brain Chemistry, Cell Adhesion, Cytoplasmic Granules, Endothelium, Vascular, Microcirculation, Neutrophils, P-Selectin, Mice

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Brain endothelium lack one of two pathways of P-selectin-mediated neutrophil adhesion

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