Apoptotic cell-derived ICAM-3 promotes both macrophage chemoattraction to and tethering of apoptotic cells

E.E. Torr, D.H. Gardner, L. Thomas, D.M. Goodall, A. Bielemeier, R. Willetts, H.R. Griffiths, L.J. Marshall, A. Devitt

Research output: Contribution to journalArticle

Abstract

A wide range of molecules acting as apoptotic cell-associated ligands, phagocyte-associated receptors or soluble bridging molecules have been implicated within the complex sequential processes that result in phagocytosis and degradation of apoptotic cells. Intercellular adhesion molecule 3 (ICAM-3, also known as CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously been implicated in apoptotic cell clearance, although its precise role in the clearance process is ill defined. The main objective of this work is to further characterise the function of ICAM-3 in the removal of apoptotic cells. Using a range of novel anti-ICAM-3 monoclonal antibodies (mAbs), including one (MA4) that blocks apoptotic cell clearance by macrophages, alongside apoptotic human leukocytes that are normal or deficient for ICAM-3, we demonstrate that ICAM-3 promotes a domain 1-2-dependent tethering interaction with phagocytes. Furthermore, we demonstrate an apoptosis-associated reduction in ICAM-3 that results from release of ICAM-3 within microparticles that potently attract macrophages to apoptotic cells. Taken together, these data suggest that apoptotic cell-derived microparticles bearing ICAM-3 promote macrophage chemoattraction to sites of leukocyte cell death and that ICAM-3 mediates subsequent cell corpse tethering to macrophages. The defined function of ICAM-3 in these processes and profound defect in chemotaxis noted to ICAM-3-deficient microparticles suggest that ICAM-3 may be an important adhesion molecule involved in chemotaxis to apoptotic human leukocytes.
LanguageEnglish
Pages671-679
Number of pages9
JournalCell Death and Differentiation
Volume19
Issue number4
Early online date25 Nov 2011
DOIs
Publication statusPublished - Apr 2012

Fingerprint

Macrophages
Leukocytes
Chemotaxis
Phagocytes
Cell-Derived Microparticles
Cell Adhesion Molecules
Cadaver
Phagocytosis
Immunoglobulins
Cell Death
Monoclonal Antibodies
Apoptosis
Ligands

Bibliographical note

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivative Works 3.0 Unported License.
To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

Keywords

  • monocytes
  • macrophages
  • ICAM-3
  • apoptosis
  • inflammation
  • chemotaxis
  • phagocytosis
  • HeLa Cells
  • Jurkat Cells

Cite this

Torr, E.E. ; Gardner, D.H. ; Thomas, L. ; Goodall, D.M. ; Bielemeier, A. ; Willetts, R. ; Griffiths, H.R. ; Marshall, L.J. ; Devitt, A. / Apoptotic cell-derived ICAM-3 promotes both macrophage chemoattraction to and tethering of apoptotic cells. In: Cell Death and Differentiation. 2012 ; Vol. 19, No. 4. pp. 671-679.
@article{0e8d7b674e1c46c7989dd126ea395430,
title = "Apoptotic cell-derived ICAM-3 promotes both macrophage chemoattraction to and tethering of apoptotic cells",
abstract = "A wide range of molecules acting as apoptotic cell-associated ligands, phagocyte-associated receptors or soluble bridging molecules have been implicated within the complex sequential processes that result in phagocytosis and degradation of apoptotic cells. Intercellular adhesion molecule 3 (ICAM-3, also known as CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously been implicated in apoptotic cell clearance, although its precise role in the clearance process is ill defined. The main objective of this work is to further characterise the function of ICAM-3 in the removal of apoptotic cells. Using a range of novel anti-ICAM-3 monoclonal antibodies (mAbs), including one (MA4) that blocks apoptotic cell clearance by macrophages, alongside apoptotic human leukocytes that are normal or deficient for ICAM-3, we demonstrate that ICAM-3 promotes a domain 1-2-dependent tethering interaction with phagocytes. Furthermore, we demonstrate an apoptosis-associated reduction in ICAM-3 that results from release of ICAM-3 within microparticles that potently attract macrophages to apoptotic cells. Taken together, these data suggest that apoptotic cell-derived microparticles bearing ICAM-3 promote macrophage chemoattraction to sites of leukocyte cell death and that ICAM-3 mediates subsequent cell corpse tethering to macrophages. The defined function of ICAM-3 in these processes and profound defect in chemotaxis noted to ICAM-3-deficient microparticles suggest that ICAM-3 may be an important adhesion molecule involved in chemotaxis to apoptotic human leukocytes.",
keywords = "monocytes, macrophages, ICAM-3, apoptosis, inflammation, chemotaxis, phagocytosis, HeLa Cells, Jurkat Cells",
author = "E.E. Torr and D.H. Gardner and L. Thomas and D.M. Goodall and A. Bielemeier and R. Willetts and H.R. Griffiths and L.J. Marshall and A. Devitt",
note = "This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/",
year = "2012",
month = "4",
doi = "10.1038/cdd.2011.167",
language = "English",
volume = "19",
pages = "671--679",
journal = "Cell Death and Differentiation",
issn = "1350-9047",
publisher = "Nature Publishing Group",
number = "4",

}

Torr, EE, Gardner, DH, Thomas, L, Goodall, DM, Bielemeier, A, Willetts, R, Griffiths, HR, Marshall, LJ & Devitt, A 2012, 'Apoptotic cell-derived ICAM-3 promotes both macrophage chemoattraction to and tethering of apoptotic cells' Cell Death and Differentiation, vol. 19, no. 4, pp. 671-679. https://doi.org/10.1038/cdd.2011.167

Apoptotic cell-derived ICAM-3 promotes both macrophage chemoattraction to and tethering of apoptotic cells. / Torr, E.E.; Gardner, D.H.; Thomas, L.; Goodall, D.M.; Bielemeier, A.; Willetts, R.; Griffiths, H.R.; Marshall, L.J.; Devitt, A.

In: Cell Death and Differentiation, Vol. 19, No. 4, 04.2012, p. 671-679.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Apoptotic cell-derived ICAM-3 promotes both macrophage chemoattraction to and tethering of apoptotic cells

AU - Torr, E.E.

AU - Gardner, D.H.

AU - Thomas, L.

AU - Goodall, D.M.

AU - Bielemeier, A.

AU - Willetts, R.

AU - Griffiths, H.R.

AU - Marshall, L.J.

AU - Devitt, A.

N1 - This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

PY - 2012/4

Y1 - 2012/4

N2 - A wide range of molecules acting as apoptotic cell-associated ligands, phagocyte-associated receptors or soluble bridging molecules have been implicated within the complex sequential processes that result in phagocytosis and degradation of apoptotic cells. Intercellular adhesion molecule 3 (ICAM-3, also known as CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously been implicated in apoptotic cell clearance, although its precise role in the clearance process is ill defined. The main objective of this work is to further characterise the function of ICAM-3 in the removal of apoptotic cells. Using a range of novel anti-ICAM-3 monoclonal antibodies (mAbs), including one (MA4) that blocks apoptotic cell clearance by macrophages, alongside apoptotic human leukocytes that are normal or deficient for ICAM-3, we demonstrate that ICAM-3 promotes a domain 1-2-dependent tethering interaction with phagocytes. Furthermore, we demonstrate an apoptosis-associated reduction in ICAM-3 that results from release of ICAM-3 within microparticles that potently attract macrophages to apoptotic cells. Taken together, these data suggest that apoptotic cell-derived microparticles bearing ICAM-3 promote macrophage chemoattraction to sites of leukocyte cell death and that ICAM-3 mediates subsequent cell corpse tethering to macrophages. The defined function of ICAM-3 in these processes and profound defect in chemotaxis noted to ICAM-3-deficient microparticles suggest that ICAM-3 may be an important adhesion molecule involved in chemotaxis to apoptotic human leukocytes.

AB - A wide range of molecules acting as apoptotic cell-associated ligands, phagocyte-associated receptors or soluble bridging molecules have been implicated within the complex sequential processes that result in phagocytosis and degradation of apoptotic cells. Intercellular adhesion molecule 3 (ICAM-3, also known as CD50), a human leukocyte-restricted immunoglobulin super-family (IgSF) member, has previously been implicated in apoptotic cell clearance, although its precise role in the clearance process is ill defined. The main objective of this work is to further characterise the function of ICAM-3 in the removal of apoptotic cells. Using a range of novel anti-ICAM-3 monoclonal antibodies (mAbs), including one (MA4) that blocks apoptotic cell clearance by macrophages, alongside apoptotic human leukocytes that are normal or deficient for ICAM-3, we demonstrate that ICAM-3 promotes a domain 1-2-dependent tethering interaction with phagocytes. Furthermore, we demonstrate an apoptosis-associated reduction in ICAM-3 that results from release of ICAM-3 within microparticles that potently attract macrophages to apoptotic cells. Taken together, these data suggest that apoptotic cell-derived microparticles bearing ICAM-3 promote macrophage chemoattraction to sites of leukocyte cell death and that ICAM-3 mediates subsequent cell corpse tethering to macrophages. The defined function of ICAM-3 in these processes and profound defect in chemotaxis noted to ICAM-3-deficient microparticles suggest that ICAM-3 may be an important adhesion molecule involved in chemotaxis to apoptotic human leukocytes.

KW - monocytes

KW - macrophages

KW - ICAM-3

KW - apoptosis

KW - inflammation

KW - chemotaxis

KW - phagocytosis

KW - HeLa Cells

KW - Jurkat Cells

UR - http://www.scopus.com/inward/record.url?scp=84858160003&partnerID=8YFLogxK

U2 - 10.1038/cdd.2011.167

DO - 10.1038/cdd.2011.167

M3 - Article

VL - 19

SP - 671

EP - 679

JO - Cell Death and Differentiation

T2 - Cell Death and Differentiation

JF - Cell Death and Differentiation

SN - 1350-9047

IS - 4

ER -