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Thomas Boesen

Shedding of Large Functionally Active CD11/CD18 Integrin Complexes from Leukocyte Membranes during Synovial Inflammation Distinguishes Three Types of Arthritis through Differential Epitope Exposure

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Shedding of Large Functionally Active CD11/CD18 Integrin Complexes from Leukocyte Membranes during Synovial Inflammation Distinguishes Three Types of Arthritis through Differential Epitope Exposure. / Gjelstrup, Louise Carstensen; Boesen, Thomas; Kragstrup, Tue Wenzel; Jørgensen, A.; Klein, Nigel J; Thiel, Steffen; Deleuran, Bent; Vorup-Jensen, Thomas.

I: Journal of Immunology, Bind 185, Nr. 7, 2010, s. 4154-68.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{64fe3a50c7cd11df8cb9000ea68e967b,
title = "Shedding of Large Functionally Active CD11/CD18 Integrin Complexes from Leukocyte Membranes during Synovial Inflammation Distinguishes Three Types of Arthritis through Differential Epitope Exposure",
abstract = "CD18 integrins are adhesion molecules expressed on the cell surface of leukocytes and play a central role in the molecular mechanisms supporting leukocyte migration to zones of inflammation. Recently, it was discovered that CD11a/CD18 is shed from the leukocyte surface in models of inflammation. In this study, we show that shedding of human CD11/CD18 complexes is a part of synovial inflammation in rheumatoid arthritis and spondyloarthritis but not in osteoarthritis. In vivo and in vitro data suggest that the shedding is driven by TNF-α, which links the process to central events in the inflammatory response. The shed complexes contain multiple heterodimers of CD11/CD18, are variable in size, and differ according to the type of synovial inflammation. Furthermore, the differential structures determine the avidity of binding of the complexes to the ICAM-1. With the estimated concentrations of CD11/CD18 in plasma and synovial fluid a significant coverage of binding sites in ICAM-1 for CD18 integrins is expected. Based on cell adhesion experiments in vitro, we hypothesize that the large soluble complexes of CD11/CD18 act in vivo to buffer leukocyte adhesion by competing with the membrane-bound receptors for ICAM-1 binding sites. As reported here for synovial inflammation changes in the concentration or structure of these complexes should be considered as likely contributors to disease activity.",
author = "Gjelstrup, {Louise Carstensen} and Thomas Boesen and Kragstrup, {Tue Wenzel} and A. J{\o}rgensen and Klein, {Nigel J} and Steffen Thiel and Bent Deleuran and Thomas Vorup-Jensen",
year = "2010",
doi = "10.4049/jimmunol.1000952",
language = "English",
volume = "185",
pages = "4154--68",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "7",

}

RIS

TY - JOUR

T1 - Shedding of Large Functionally Active CD11/CD18 Integrin Complexes from Leukocyte Membranes during Synovial Inflammation Distinguishes Three Types of Arthritis through Differential Epitope Exposure

AU - Gjelstrup, Louise Carstensen

AU - Boesen, Thomas

AU - Kragstrup, Tue Wenzel

AU - Jørgensen, A.

AU - Klein, Nigel J

AU - Thiel, Steffen

AU - Deleuran, Bent

AU - Vorup-Jensen, Thomas

PY - 2010

Y1 - 2010

N2 - CD18 integrins are adhesion molecules expressed on the cell surface of leukocytes and play a central role in the molecular mechanisms supporting leukocyte migration to zones of inflammation. Recently, it was discovered that CD11a/CD18 is shed from the leukocyte surface in models of inflammation. In this study, we show that shedding of human CD11/CD18 complexes is a part of synovial inflammation in rheumatoid arthritis and spondyloarthritis but not in osteoarthritis. In vivo and in vitro data suggest that the shedding is driven by TNF-α, which links the process to central events in the inflammatory response. The shed complexes contain multiple heterodimers of CD11/CD18, are variable in size, and differ according to the type of synovial inflammation. Furthermore, the differential structures determine the avidity of binding of the complexes to the ICAM-1. With the estimated concentrations of CD11/CD18 in plasma and synovial fluid a significant coverage of binding sites in ICAM-1 for CD18 integrins is expected. Based on cell adhesion experiments in vitro, we hypothesize that the large soluble complexes of CD11/CD18 act in vivo to buffer leukocyte adhesion by competing with the membrane-bound receptors for ICAM-1 binding sites. As reported here for synovial inflammation changes in the concentration or structure of these complexes should be considered as likely contributors to disease activity.

AB - CD18 integrins are adhesion molecules expressed on the cell surface of leukocytes and play a central role in the molecular mechanisms supporting leukocyte migration to zones of inflammation. Recently, it was discovered that CD11a/CD18 is shed from the leukocyte surface in models of inflammation. In this study, we show that shedding of human CD11/CD18 complexes is a part of synovial inflammation in rheumatoid arthritis and spondyloarthritis but not in osteoarthritis. In vivo and in vitro data suggest that the shedding is driven by TNF-α, which links the process to central events in the inflammatory response. The shed complexes contain multiple heterodimers of CD11/CD18, are variable in size, and differ according to the type of synovial inflammation. Furthermore, the differential structures determine the avidity of binding of the complexes to the ICAM-1. With the estimated concentrations of CD11/CD18 in plasma and synovial fluid a significant coverage of binding sites in ICAM-1 for CD18 integrins is expected. Based on cell adhesion experiments in vitro, we hypothesize that the large soluble complexes of CD11/CD18 act in vivo to buffer leukocyte adhesion by competing with the membrane-bound receptors for ICAM-1 binding sites. As reported here for synovial inflammation changes in the concentration or structure of these complexes should be considered as likely contributors to disease activity.

U2 - 10.4049/jimmunol.1000952

DO - 10.4049/jimmunol.1000952

M3 - Journal article

C2 - 20826754

VL - 185

SP - 4154

EP - 4168

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -