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The disintegrin-like metalloproteinase ADAM 10 is involved in coinstitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion. / Hundhausen, C.; Misztela, D.; Berkhout, Theo; Broadway, N.; Saftig, P.; Reiss, K.; Hartmann, D.; Fahrenholz, F.; Postina, R.; Matthews, J.; Kallen, K.J.; Rose-John, S.; Ludwig, A.

In: Blood Purification, Vol. 102, No. 4, 15.08.2003, p. 1186-1195.

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Harvard

Hundhausen, C, Misztela, D, Berkhout, T, Broadway, N, Saftig, P, Reiss, K, Hartmann, D, Fahrenholz, F, Postina, R, Matthews, J, Kallen, KJ, Rose-John, S & Ludwig, A 2003, 'The disintegrin-like metalloproteinase ADAM 10 is involved in coinstitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion', Blood Purification, vol. 102, no. 4, pp. 1186-1195. https://doi.org/10.1182/blood-2002-12-3775

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Vancouver

Author

Hundhausen, C. ; Misztela, D. ; Berkhout, Theo ; Broadway, N. ; Saftig, P. ; Reiss, K. ; Hartmann, D. ; Fahrenholz, F. ; Postina, R. ; Matthews, J. ; Kallen, K.J. ; Rose-John, S. ; Ludwig, A. / The disintegrin-like metalloproteinase ADAM 10 is involved in coinstitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion. In: Blood Purification. 2003 ; Vol. 102, No. 4. pp. 1186-1195.

Bibtex

@article{5983f029562f4b1d92aab0bfb7b8ecee,
title = "The disintegrin-like metalloproteinase ADAM 10 is involved in coinstitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion",
abstract = "The CX3C chemokine fractalkine (CX3CL1) exists as a membrane-expressed protein promoting cell-cell adhesion and as a soluble molecule inducing chemotaxis. Transmembrane CX3CL1 is converted into its soluble form by defined proteolytic cleavage (shedding), which can be enhanced by stimulation withphorbol-12-myristate-13-acetate (PMA). PMA-induced CX3CL1 shedding has been shown to involve the tumor necrosis factor-alpha-converting enzyme (TACE), whereas the constitutive cleavage in unstimulated cells remains elusive. Here we demonstrate a role of the closely related disintegrin-like metalloproteinase 10 (ADAM10) in the constitutive CX3CL1 cleavage. The hydroxamate GW280264X, capable of blocking TACE as Well as ADAM10, proved to be an effective inhibitor of the constitutive and the PMA-inducible CX3CL1 cleavage in CX3CL-expressing ECV-304 cells (CX3CL1-ECV-304), whereas GI254023X, preferentially blocking ADAM10 but not TACE, reduced the constitutive, cleavage only. Overexpression of ADAM10 in COS-7 cells enhanced constitutive cleavage of CX3CL1 and, more importantly, in murine fibroblasts deficient of ADAM10 constitutive CX3CL1 cleavage was markedly reduced. Thus, ADAM10 contributes to the constitutive shedding of CX3CL1 in un-stimulated cells. Addressing the functional role of CX3CL1 shedding for the adhesion of monocytic cells via membrane-expressed CX3CL1, we found that THP-1 cells adhere to CX3CL1-ECV-304 cells but detach in the course of vigorous washing. Inhibition of ADAM10-mediated CX3CL1 shedding not only increased adhesive properties of CX3CL1-ECV-304 cells but also prevented de-adhesion of bound THP-1 cells. Our data demonstrate that ADAM10 is involved in the constitutive cleavage of CX3CL1 and thereby may regulate the recruitment of monocytic cells to CX3CL1-expressing cell layers. (C) 2003 by The American Society of Hematology.",
keywords = "CONVERTING-ENZYME, NECROSIS-FACTOR-ALPHA, TARGETED DELETION, ENDOTHELIAL-CELLS, MACROPHAGE-DERIVED CHEMOKINE, TNF-ALPHA, RECEPTOR CX(3)CR1, DENDRITIC CELLS, SECRETASE CLEAVAGE, IN-VIVO",
author = "C. Hundhausen and D. Misztela and Theo Berkhout and N. Broadway and P. Saftig and K. Reiss and D. Hartmann and F. Fahrenholz and R. Postina and J. Matthews and K.J. Kallen and S. Rose-John and A. Ludwig",
year = "2003",
month = "8",
day = "15",
doi = "10.1182/blood-2002-12-3775",
language = "English",
volume = "102",
pages = "1186--1195",
journal = "Blood Purification",
issn = "0253-5068",
publisher = "S. Karger AG",
number = "4",

}

RIS

TY - JOUR

T1 - The disintegrin-like metalloproteinase ADAM 10 is involved in coinstitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion

AU - Hundhausen, C.

AU - Misztela, D.

AU - Berkhout, Theo

AU - Broadway, N.

AU - Saftig, P.

AU - Reiss, K.

AU - Hartmann, D.

AU - Fahrenholz, F.

AU - Postina, R.

AU - Matthews, J.

AU - Kallen, K.J.

AU - Rose-John, S.

AU - Ludwig, A.

PY - 2003/8/15

Y1 - 2003/8/15

N2 - The CX3C chemokine fractalkine (CX3CL1) exists as a membrane-expressed protein promoting cell-cell adhesion and as a soluble molecule inducing chemotaxis. Transmembrane CX3CL1 is converted into its soluble form by defined proteolytic cleavage (shedding), which can be enhanced by stimulation withphorbol-12-myristate-13-acetate (PMA). PMA-induced CX3CL1 shedding has been shown to involve the tumor necrosis factor-alpha-converting enzyme (TACE), whereas the constitutive cleavage in unstimulated cells remains elusive. Here we demonstrate a role of the closely related disintegrin-like metalloproteinase 10 (ADAM10) in the constitutive CX3CL1 cleavage. The hydroxamate GW280264X, capable of blocking TACE as Well as ADAM10, proved to be an effective inhibitor of the constitutive and the PMA-inducible CX3CL1 cleavage in CX3CL-expressing ECV-304 cells (CX3CL1-ECV-304), whereas GI254023X, preferentially blocking ADAM10 but not TACE, reduced the constitutive, cleavage only. Overexpression of ADAM10 in COS-7 cells enhanced constitutive cleavage of CX3CL1 and, more importantly, in murine fibroblasts deficient of ADAM10 constitutive CX3CL1 cleavage was markedly reduced. Thus, ADAM10 contributes to the constitutive shedding of CX3CL1 in un-stimulated cells. Addressing the functional role of CX3CL1 shedding for the adhesion of monocytic cells via membrane-expressed CX3CL1, we found that THP-1 cells adhere to CX3CL1-ECV-304 cells but detach in the course of vigorous washing. Inhibition of ADAM10-mediated CX3CL1 shedding not only increased adhesive properties of CX3CL1-ECV-304 cells but also prevented de-adhesion of bound THP-1 cells. Our data demonstrate that ADAM10 is involved in the constitutive cleavage of CX3CL1 and thereby may regulate the recruitment of monocytic cells to CX3CL1-expressing cell layers. (C) 2003 by The American Society of Hematology.

AB - The CX3C chemokine fractalkine (CX3CL1) exists as a membrane-expressed protein promoting cell-cell adhesion and as a soluble molecule inducing chemotaxis. Transmembrane CX3CL1 is converted into its soluble form by defined proteolytic cleavage (shedding), which can be enhanced by stimulation withphorbol-12-myristate-13-acetate (PMA). PMA-induced CX3CL1 shedding has been shown to involve the tumor necrosis factor-alpha-converting enzyme (TACE), whereas the constitutive cleavage in unstimulated cells remains elusive. Here we demonstrate a role of the closely related disintegrin-like metalloproteinase 10 (ADAM10) in the constitutive CX3CL1 cleavage. The hydroxamate GW280264X, capable of blocking TACE as Well as ADAM10, proved to be an effective inhibitor of the constitutive and the PMA-inducible CX3CL1 cleavage in CX3CL-expressing ECV-304 cells (CX3CL1-ECV-304), whereas GI254023X, preferentially blocking ADAM10 but not TACE, reduced the constitutive, cleavage only. Overexpression of ADAM10 in COS-7 cells enhanced constitutive cleavage of CX3CL1 and, more importantly, in murine fibroblasts deficient of ADAM10 constitutive CX3CL1 cleavage was markedly reduced. Thus, ADAM10 contributes to the constitutive shedding of CX3CL1 in un-stimulated cells. Addressing the functional role of CX3CL1 shedding for the adhesion of monocytic cells via membrane-expressed CX3CL1, we found that THP-1 cells adhere to CX3CL1-ECV-304 cells but detach in the course of vigorous washing. Inhibition of ADAM10-mediated CX3CL1 shedding not only increased adhesive properties of CX3CL1-ECV-304 cells but also prevented de-adhesion of bound THP-1 cells. Our data demonstrate that ADAM10 is involved in the constitutive cleavage of CX3CL1 and thereby may regulate the recruitment of monocytic cells to CX3CL1-expressing cell layers. (C) 2003 by The American Society of Hematology.

KW - CONVERTING-ENZYME

KW - NECROSIS-FACTOR-ALPHA

KW - TARGETED DELETION

KW - ENDOTHELIAL-CELLS

KW - MACROPHAGE-DERIVED CHEMOKINE

KW - TNF-ALPHA

KW - RECEPTOR CX(3)CR1

KW - DENDRITIC CELLS

KW - SECRETASE CLEAVAGE

KW - IN-VIVO

U2 - 10.1182/blood-2002-12-3775

DO - 10.1182/blood-2002-12-3775

M3 - Article

VL - 102

SP - 1186

EP - 1195

JO - Blood Purification

JF - Blood Purification

SN - 0253-5068

IS - 4

ER -