Dataset Information

Endothelial ICAM-1 adhesome recruits CD44 for optimal regulation of human cytotoxic T lymphocyte extravasation

ABSTRACT: The endothelial lining of blood vessels is covered with a thin polysaccharide coat called the glycocalyx. This layer of polysaccharides contains hyaluronan that forms a protective coat on the endothelial surface. Upon inflammation, leukocytes leave the circulation and enter inflamed tissue by crossing inflamed endothelial cells, mediated by adhesion molecules such as ICAM-1/CD54. To what extent the glycocalyx participates in the regulation of leukocyte transmigration is not clear. During extravasation, leukocyte integrins cluster ICAM-1, resulting in the recruitment of a number of intracellular proteins and subsequent downstream effects in the endothelial cells. Using an unbiased proteomics approach, we identified the full ICAM-1 adhesome and identified 93 new subunits of the ICAM-1 adhesome. Interestingly, we found the glycoprotein CD44 as part of the glycocalyx to be recruited to clustered ICAM-1 specifically. Our data demonstrate that CD44 binds hyaluronan to the endothelial surface, where it locally concentrates and presents chemokines that are essential for leukocytes to cross the endothelial lining. Together, we discover a link between ICAM-1 clustering and hyaluronan-mediated chemokine presentation by recruiting hyaluronan to sites of leukocyte adhesion via CD44.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Umbilical Vein Endothelial Cell Line, Blood Vessel Endothelial Cell

DISEASE(S): Inflammation

SUBMITTER: Floris van Alphen

LAB HEAD: Prof. Dr. J.D. van Buul

PROVIDER: PXD036581 | Pride | 2025-09-30

REPOSITORIES: Pride

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Endothelial ICAM-1 Adhesome Recruits CD44 for Optimal Transcellular Migration of Human CTLs.

van Steen Abraham C I ACI Grönloh Max L B MLB Joosten Sander S van Alphen Floris F van den Biggelaar Maartje M Nolte Martijn A MA Spaargaren Marcel M van Buul Jaap D JD Schoppmeyer Rouven R

Journal of immunology (Baltimore, Md. : 1950) 20230801 3

The endothelial lining of blood vessels is covered with a thin polysaccharide coat called the glycocalyx. This layer of polysaccharides contains hyaluronan that forms a protective coat on the endothelial surface. Upon inflammation, leukocytes leave the circulation and enter inflamed tissue by crossing inflamed endothelial cells, mediated by adhesion molecules such as ICAM-1/CD54. To what extent the glycocalyx participates in the regulation of leukocyte transmigration is not clear. During extrava ...[more]

PMID: 37341500

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