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Cited by 575Cell Adhesion Molecules ResearchAtherosclerosis and Cardiovascular DiseasesChemokine receptors and signaling

Selectins: initiators of leucocyte adhesion and signalling at the vascular wall

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McEver, Rodger P.·2015·Cardiovascular Research
DOI 10.1093/cvr/cvv154PMC PMC4592324
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Abstract

The selectins are transmembrane, Ca(2+)-dependent lectins that mediate leucocyte rolling on vascular surfaces, the first adhesive step during inflammation and immune surveillance. Leucocytes express L-selectin, activated platelets express P-selectin, and activated endothelial cells express E- and P-selectin. Rolling involves force-regulated, rapidly reversible interactions of selectins with a limited number of glycosylated cell surface ligands. Rolling permits leucocytes to interact with immobilized chemokines that convert β2 integrins to high-affinity conformations, which mediate arrest, post-arrest adhesion strengthening, and transendothelial migration. However, rolling leucocytes also transduce signals through selectin ligands, the focus of this review. These signals include serial activation of kinases and recruitment of adaptors that convert integrins to intermediate-affinity conformations, which decrease rolling velocities. In vitro, selectin signalling enables myeloid cells to respond to suboptimal levels of chemokines and other agonists. This cooperative signalling triggers effector responses such as degranulation, superoxide production, chemokine synthesis, and release of procoagulant/proinflammatory microparticles. In vivo, selectin-mediated adhesion and signalling likely contributes to atherosclerosis, arterial and deep vein thrombosis, ischaemia-reperfusion injury, and other cardiovascular diseases.

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  • Selectin and galectin pathways promote feedforward stimulation of interleukin production.

    “Vascular signaling networks demonstrated marked upregulation of pro-inflammatory selectin and galectin pathways (Fig. 7, G and H, fig. S17, C and D), which promote feedforward stimulation of interleukin production (64-66).”

    From Molecular and cellular processes disrupted in the early postnatal Down syndrome prefrontal cortex (2026) · cites this paper as [66]

    The Conclusion (section 8; page unavailable) says selectin signals can enable cytokine secretion in response to other agonists, but are usually insufficient to induce it alone. The discussion of platelet–myeloid interactions describes possible feedback-loop amplification. Our copy does not connect galectin pathways to this process or specifically identify interleukin production. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • P-selectin has a role in immune cell modulation and trafficking.

    “E-selectin (SELE), a cytokine-induced endothelial adhesion molecule, was uniquely expressed in Ts21 vascular cells (Fig. 7G), whereas P-selectin signaling was elevated in microglia-vascular interactions (Fig. 7H), consistent with its role in immune cell modulation and trafficking (66).”

    From Molecular and cellular processes disrupted in the early postnatal Down syndrome prefrontal cortex (2026) · cites this paper as [66]

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Cited by

Sorted by citations

Authors
McEver, R. P.
Affiliations
Oklahoma Medical Research Foundation (US)
Corresponding author
McEver, Rodger P.
ORCID
McEver, Rodger P.
Venue
Cardiovascular Research
Publisher
Oxford University Press (OUP)
Published
2015-05-20
Volume
107
Issue
3
Pages
331-339
ISSN
  • 0008-6363 (ISSN-L)
  • 1755-3245
DOI
10.1093/cvr/cvv154
PMC
PMC4592324
OpenAlex
W1914229765
Cited by
575
References
3
Citations by year
2026: 47 · 2025: 69 · 2024: 61 · 2023: 60 · 2022: 63 · 2021: 53 · 2020: 47 · 2019: 48 · 2018: 44 · 2017: 43 · 2016: 32 · 2015: 7 · 2013: 1
FWCI
5.72
Type
journal article
Language
en
Open access
Locations
  • Cardiovascular Research (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (HL034363 and HL085607)
Topics
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Keywords
selectins, leukocyte adhesion, L-selectin, P-selectin, E-selectin, chemokines, beta2 integrins, integrin affinity, transendothelial migration, inflammation, immune surveillance, atherosclerosis, thrombosis, ischemia-reperfusion injury, microparticles, myeloid cells
MeSH terms
Animals, Blood Platelets, Blood Vessels, Humans, Ligands, Neutrophils, Signal Transduction, Selectins, Myeloid Cells, Leukocyte Rolling

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