TY - JOUR
T1 - Endothelial ICAM-1 Adhesome Recruits CD44 for Optimal Transcellular Migration of Human CTLs
AU - van Steen, Abraham C. I.
AU - Grönloh, Max L. B.
AU - Joosten, Sander
AU - van Alphen, Floris
AU - van den Biggelaar, Maartje
AU - Nolte, Martijn A.
AU - Spaargaren, Marcel
AU - van Buul, Jaap D.
AU - Schoppmeyer, Rouven
N1 - Funding Information: This work was supported by the Landsteiner Foundation for Blood Transfusion Research Grant 1649 (to A.C.I.v.S.) and by ZonMw (Netherlands Organisation for Health Research and Development) Grant 91819632 (to R.S. and J.D.v.B.). Publisher Copyright: © 2023 by TheAmericanAssociation of Immunologists, Inc.
PY - 2023/8/1
Y1 - 2023/8/1
N2 - 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. For our studies, we used primary human endothelial and immune cells. With an unbiased proteomics approach, we identified the full ICAM-1 adhesome and identified 93 (to our knowledge) 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. Taken together, we discover a link between ICAM-1 clustering and hyaluronan-mediated chemokine presentation by recruiting hyaluronan to sites of leukocyte adhesion via CD44.
AB - 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. For our studies, we used primary human endothelial and immune cells. With an unbiased proteomics approach, we identified the full ICAM-1 adhesome and identified 93 (to our knowledge) 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. Taken together, we discover a link between ICAM-1 clustering and hyaluronan-mediated chemokine presentation by recruiting hyaluronan to sites of leukocyte adhesion via CD44.
UR - http://www.scopus.com/inward/record.url?scp=85165221926&partnerID=8YFLogxK
U2 - https://doi.org/10.4049/jimmunol.2200761
DO - https://doi.org/10.4049/jimmunol.2200761
M3 - Article
C2 - 37341500
SN - 0022-1767
VL - 211
SP - 377
EP - 388
JO - Journal of immunology (Baltimore, Md.
JF - Journal of immunology (Baltimore, Md.
IS - 3
ER -