Apoptotic
 cell‐associated 
ICAM‐3 
in 
the 
phagocytic 
removal 
of 
apoptotic 
cells


E.E. Torr, Leanne Thomas, D.H. Gardner, Andrew Devitt

Research output: Contribution to conferencePoster

Abstract

Apoptosis is a highly controlled cell death programme that culminates in the exposure of molecular ‘flags’ at the dying cell surface that permit recognition and removal by viable phagocytes. Failure to efficiently remove dying cells can lead to devastating inflammatory and autoimmune disorders.
The molecular mechanisms underlying apoptotic cell surface changes are poorly understood. Our previous work has shown an apoptosis-associated functional change in ICAM-3 (a heavily glycosylated, leukocyte-restricted Immunoglobulin Super-Family member) resulting in a molecular ‘flag’ to mediate corpse removal.
Here we detail apoptosis-associated changes in ICAM-3 and define their role in ICAM-3’s novel function in apoptotic cell clearance. We show ICAM-3 functions to tether apoptotic leukocytes to macrophages via an undefined receptor. Though CD14 has been suggested as a possible receptor for apoptotic cell-associated ICAM-3, we demonstrate ICAM-3 functions for apoptotic cell clearance in the absence of CD14. Furthermore, we demonstrate leukocytes display early changes in cell surface glycosylation and a marked reduction in ICAM-3, a change that correlates reduced cell volume throughout apoptosis. This loss of ICAM-3 occurs via shedding of ICAM-3 in microparticles (‘apoptotic bodies’). Such microparticles are potent chemoattractants for macrophages. Notably, microparticles from ICAM-3-deficient leukocytes are significantly less chemoattractive than microparticles from their ICAM-3-replete counterparts.
These data support the hypothesis that ICAM-3 acts as an apoptotic cell-associated ligand to tether dying cells to phagocytes in a CD14-independent manner. Furthermore our data suggest that released ICAM-3 may promote the recruitment of phagocytes to sites of apoptosis.
LanguageEnglish
Publication statusPublished - 3 Dec 2010
Event2010 British Society for Immunology Annual Congress - Liverpool, United Kingdom
Duration: 6 Dec 201010 Dec 2010
http://www.immunology.org/page.aspx?pid=1519

Conference

Conference2010 British Society for Immunology Annual Congress
CountryUnited Kingdom
CityLiverpool
Period6/12/1010/12/10
Internet address

Fingerprint

Apoptosis
Leukocytes
Phagocytes
Macrophages
Chemotactic Factors
Glycosylation
Cell Size
Cadaver
Immunoglobulins
Cell Death
Ligands

Bibliographical note

Abstract published: Immunology (2010), Abstracts selected for poster presentations. Immunology, 131 (s1): 120–123. doi: 10.1111/j.1365-2567.2010.03390.x

Cite this

Torr, E. E., Thomas, L., Gardner, D. H., & Devitt, A. (2010). Apoptotic
 cell‐associated 
ICAM‐3 
in 
the 
phagocytic 
removal 
of 
apoptotic 
cells
. Poster session presented at 2010 British Society for Immunology Annual Congress, Liverpool, United Kingdom.
Torr, E.E. ; Thomas, Leanne ; Gardner, D.H. ; Devitt, Andrew. / Apoptotic
 cell‐associated 
ICAM‐3 
in 
the 
phagocytic 
removal 
of 
apoptotic 
cells
. Poster session presented at 2010 British Society for Immunology Annual Congress, Liverpool, United Kingdom.
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title = "Apoptotic
 cell‐associated 
ICAM‐3 
in 
the 
phagocytic 
removal 
of 
apoptotic 
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",
abstract = "Apoptosis is a highly controlled cell death programme that culminates in the exposure of molecular ‘flags’ at the dying cell surface that permit recognition and removal by viable phagocytes. Failure to efficiently remove dying cells can lead to devastating inflammatory and autoimmune disorders.The molecular mechanisms underlying apoptotic cell surface changes are poorly understood. Our previous work has shown an apoptosis-associated functional change in ICAM-3 (a heavily glycosylated, leukocyte-restricted Immunoglobulin Super-Family member) resulting in a molecular ‘flag’ to mediate corpse removal.Here we detail apoptosis-associated changes in ICAM-3 and define their role in ICAM-3’s novel function in apoptotic cell clearance. We show ICAM-3 functions to tether apoptotic leukocytes to macrophages via an undefined receptor. Though CD14 has been suggested as a possible receptor for apoptotic cell-associated ICAM-3, we demonstrate ICAM-3 functions for apoptotic cell clearance in the absence of CD14. Furthermore, we demonstrate leukocytes display early changes in cell surface glycosylation and a marked reduction in ICAM-3, a change that correlates reduced cell volume throughout apoptosis. This loss of ICAM-3 occurs via shedding of ICAM-3 in microparticles (‘apoptotic bodies’). Such microparticles are potent chemoattractants for macrophages. Notably, microparticles from ICAM-3-deficient leukocytes are significantly less chemoattractive than microparticles from their ICAM-3-replete counterparts.These data support the hypothesis that ICAM-3 acts as an apoptotic cell-associated ligand to tether dying cells to phagocytes in a CD14-independent manner. Furthermore our data suggest that released ICAM-3 may promote the recruitment of phagocytes to sites of apoptosis.",
author = "E.E. Torr and Leanne Thomas and D.H. Gardner and Andrew Devitt",
note = "Abstract published: Immunology (2010), Abstracts selected for poster presentations. Immunology, 131 (s1): 120–123. doi: 10.1111/j.1365-2567.2010.03390.x; 2010 British Society for Immunology Annual Congress ; Conference date: 06-12-2010 Through 10-12-2010",
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Torr, EE, Thomas, L, Gardner, DH & Devitt, A 2010, 'Apoptotic
 cell‐associated 
ICAM‐3 
in 
the 
phagocytic 
removal 
of 
apoptotic 
cells
' 2010 British Society for Immunology Annual Congress, Liverpool, United Kingdom, 6/12/10 - 10/12/10, .

Apoptotic
 cell‐associated 
ICAM‐3 
in 
the 
phagocytic 
removal 
of 
apoptotic 
cells
. / Torr, E.E.; Thomas, Leanne; Gardner, D.H.; Devitt, Andrew.

2010. Poster session presented at 2010 British Society for Immunology Annual Congress, Liverpool, United Kingdom.

Research output: Contribution to conferencePoster

TY - CONF

T1 - Apoptotic
 cell‐associated 
ICAM‐3 
in 
the 
phagocytic 
removal 
of 
apoptotic 
cells


AU - Torr, E.E.

AU - Thomas, Leanne

AU - Gardner, D.H.

AU - Devitt, Andrew

N1 - Abstract published: Immunology (2010), Abstracts selected for poster presentations. Immunology, 131 (s1): 120–123. doi: 10.1111/j.1365-2567.2010.03390.x

PY - 2010/12/3

Y1 - 2010/12/3

N2 - Apoptosis is a highly controlled cell death programme that culminates in the exposure of molecular ‘flags’ at the dying cell surface that permit recognition and removal by viable phagocytes. Failure to efficiently remove dying cells can lead to devastating inflammatory and autoimmune disorders.The molecular mechanisms underlying apoptotic cell surface changes are poorly understood. Our previous work has shown an apoptosis-associated functional change in ICAM-3 (a heavily glycosylated, leukocyte-restricted Immunoglobulin Super-Family member) resulting in a molecular ‘flag’ to mediate corpse removal.Here we detail apoptosis-associated changes in ICAM-3 and define their role in ICAM-3’s novel function in apoptotic cell clearance. We show ICAM-3 functions to tether apoptotic leukocytes to macrophages via an undefined receptor. Though CD14 has been suggested as a possible receptor for apoptotic cell-associated ICAM-3, we demonstrate ICAM-3 functions for apoptotic cell clearance in the absence of CD14. Furthermore, we demonstrate leukocytes display early changes in cell surface glycosylation and a marked reduction in ICAM-3, a change that correlates reduced cell volume throughout apoptosis. This loss of ICAM-3 occurs via shedding of ICAM-3 in microparticles (‘apoptotic bodies’). Such microparticles are potent chemoattractants for macrophages. Notably, microparticles from ICAM-3-deficient leukocytes are significantly less chemoattractive than microparticles from their ICAM-3-replete counterparts.These data support the hypothesis that ICAM-3 acts as an apoptotic cell-associated ligand to tether dying cells to phagocytes in a CD14-independent manner. Furthermore our data suggest that released ICAM-3 may promote the recruitment of phagocytes to sites of apoptosis.

AB - Apoptosis is a highly controlled cell death programme that culminates in the exposure of molecular ‘flags’ at the dying cell surface that permit recognition and removal by viable phagocytes. Failure to efficiently remove dying cells can lead to devastating inflammatory and autoimmune disorders.The molecular mechanisms underlying apoptotic cell surface changes are poorly understood. Our previous work has shown an apoptosis-associated functional change in ICAM-3 (a heavily glycosylated, leukocyte-restricted Immunoglobulin Super-Family member) resulting in a molecular ‘flag’ to mediate corpse removal.Here we detail apoptosis-associated changes in ICAM-3 and define their role in ICAM-3’s novel function in apoptotic cell clearance. We show ICAM-3 functions to tether apoptotic leukocytes to macrophages via an undefined receptor. Though CD14 has been suggested as a possible receptor for apoptotic cell-associated ICAM-3, we demonstrate ICAM-3 functions for apoptotic cell clearance in the absence of CD14. Furthermore, we demonstrate leukocytes display early changes in cell surface glycosylation and a marked reduction in ICAM-3, a change that correlates reduced cell volume throughout apoptosis. This loss of ICAM-3 occurs via shedding of ICAM-3 in microparticles (‘apoptotic bodies’). Such microparticles are potent chemoattractants for macrophages. Notably, microparticles from ICAM-3-deficient leukocytes are significantly less chemoattractive than microparticles from their ICAM-3-replete counterparts.These data support the hypothesis that ICAM-3 acts as an apoptotic cell-associated ligand to tether dying cells to phagocytes in a CD14-independent manner. Furthermore our data suggest that released ICAM-3 may promote the recruitment of phagocytes to sites of apoptosis.

M3 - Poster

ER -

Torr EE, Thomas L, Gardner DH, Devitt A. Apoptotic
 cell‐associated 
ICAM‐3 
in 
the 
phagocytic 
removal 
of 
apoptotic 
cells
. 2010. Poster session presented at 2010 British Society for Immunology Annual Congress, Liverpool, United Kingdom.