CoChat
Sign Up
Cited by 245Cell Adhesion Molecules ResearchMultiple Sclerosis Research StudiesNeuroinflammation and Neurodegeneration Mechanisms

Molecular Mechanisms Involved in Lymphocyte Recruitment in Inflamed Brain Microvessels: Critical Roles for P-Selectin Glycoprotein Ligand-1 and Heterotrimeric Gi-Linked Receptors

Open access
Piccio, Laura, Rossi, Barbara, Scarpini, Elio, Laudanna, Carlo, Giagulli, Cinzia, Issekutz, Andrew C, Vestweber, Dietmar, Butcher, Eugene C +1 more·2002·The Journal of Immunology
DOI 10.4049/jimmunol.168.4.1940
Open this paper in CoChat — free accountOpen PDF

Abstract

Lymphocyte recruitment into the brain is a critical event in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis. We developed a novel intravital microscopy model to directly analyze through the skull the interactions between lymphocytes and the endothelium in cerebral venules of mice. No adhesive interactions were observed between lymphocytes and the nonactivated endothelium in the cerebral microcirculation. When brain venules were activated by pretreating mice with TNF-α or LPS, proteolipid protein 139–151 autoreactive T lymphocytes rolled and arrested; notably, only a few peripheral lymph node cells rolled and firmly adhered. Abs anti-P-selectin glycoprotein ligand-1 and anti-E- and P-selectin blocked tethering and rolling of autoreactive lymphocytes, suggesting that P-selectin glycoprotein ligand-1/endothelial selectins are critical in the recruitment of lymphocytes in inflamed brain venules. E- and P-selectin were expressed on cerebral vessels upon in vivo activation and had a patchy distribution during the preclinical phase of active and passive experimental autoimmune encephalomyelitis. LFA-1/ICAM-1 and α4 integrins/VCAM-1 supported rolling, but were not relevant to rolling velocity. Firm arrest was mainly mediated by LFA-1 and ICAM-1. Pretreatment of autoreactive lymphocytes with pertussis toxin blocked integrin-dependent arrest, implicating a requirement for Gi protein-dependent signaling in vessels from nonlymphoid districts. In conclusion, our data unveils the molecular mechanisms controlling the recruitment of autoreactive lymphocytes in inflamed cerebral vessels and suggest new insights into the pathogenesis of autoimmune inflammatory diseases of the CNS.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.4049/jimmunol.168.4.1940

Cites

57 of 57 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • T cell rolling and eventual arrest during EAE is mediated by LFA-1-ICAM-1 and VLA-4-VCAM-1 interactions.

    “This results in T cell rolling and eventual arrest mediated by LFA-1-ICAM-1 and VLA-4-VCAM-1 interactions (Fig. 4), as observed by using the proteolipid protein (PLP139-151) immunization model of EAE (110).”

    From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [110]

  • During CNS autoimmune disease, the process of diapedesis involves T cell interactions with endothelial selectins through P-selectin glycoprotein ligand-1 (PSGL-1), although the requirement for selectins is not absolute.

    “Similar to steady state, the process of diapedesis during CNS autoimmune disease involves T cell interactions with endothelial selectins through P-selectin glycoprotein ligand–1 (PSGL-1), although the requirement for selectins is not absolute.”

    From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [110]

  • T cell arrest during EAE is often linked to G protein signaling in vessels, facilitated by chemokines such as CCL19 and CCL21 produced by vascular endothelial cells.

    “In addition to adhesion molecules, T cell arrest is often linked to G protein signaling in vessels (110), which is facilitated by chemokines such as CCL19 and CCL21 that are produced by vascular endothelial cells (113).”

    From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [110]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Piccio, L., Rossi, B., Scarpini, E., Laudanna, C., Giagulli, C., Issekutz, A. C., Vestweber, D., Butcher, E. C., & Constantin, G.
Affiliations
  • University of Verona (IT)
  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
  • Dalhousie University (CA)
  • University of Münster (DE)
  • Stanford University (US)
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2002-02
Volume
168
Issue
4
Pages
1940-1949
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.168.4.1940
OpenAlex
W1960336193
Cited by
245
References
56
Citations by year
2026: 4 · 2025: 2 · 2024: 5 · 2023: 7 · 2022: 9 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 2 · 2017: 7 · 2016: 7 · 2015: 12 · 2014: 11 · 2013: 8 · 2012: 16
FWCI
9.00
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • INFM-OAR (INFN Catania) (submittedVersion, other-oa)
Funders
  • Fondazione Italiana Sclerosi Multipla
  • Deutsche Forschungsgemeinschaft
  • Consiglio Nazionale delle Ricerche
Topics
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
lymphocyte recruitment, PSGL-1, E-selectin, P-selectin, endothelial activation, multiple sclerosis, experimental autoimmune encephalomyelitis, autoreactive T cells, heterotrimeric G protein signaling, pertussis toxin, intravital microscopy, TNF-α, LPS, lymphocyte-endothelial interactions
MeSH terms
Animals, Autoantigens, Brain, Cell Movement, Cerebrovascular Circulation, Encephalomyelitis, Autoimmune, Experimental, Endothelium, Vascular, Female, Hemodynamics, Membrane Glycoproteins, Microcirculation, Microscopy, Fluorescence, Receptors, Cell Surface, T-Lymphocytes, Venules, Cell Adhesion Molecules, Integrins, Models, Immunological, Selectins, GTP-Binding Protein alpha Subunits, Gi-Go, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review