Characterization of tissue transglutaminase 2 in macrophage function

Vinod Nadella, Vivian Wang, Martin Griffin, Andrew Devitt

Research output: Contribution to conferencePoster

Abstract

Programmed cell death, apoptosis, is a highly regulated process that removes damaged or unwanted cells in vivo and has significant immunological implications. Defective clearance of apoptotic cells by macrophages (professional phagocytes) is known to result in chronic inflammatory and autoimmune disease.

Tissue transglutaminase 2 (TG2) is a Ca2+-dependent protein cross linking enzyme known to play an important role in a number of cell functions. Up-regulation of TG2 is thought to be involved in monocyte to macrophage differentiation and defective clearance of apoptotic cells by TG2 null mice has been described though in this context the role of TG2 is yet to be fully elucidated. Cell surface-associated TG2 is now recognized as being important in regulating cell adhesion and migration, via its association with cell surface receptors such as syndecan-4, ß1 and ß3 integrin, but its extracellular role in the clearance of apoptotic cells is still not fully explored.

Our work aims to characterize the role of TG2 and its partners (e.g. syndecan-4 and ß3 integrin) in macrophage function within the framework of apoptotic cell clearance. Both THP-1 cell-derived macrophage-like cells and primary human macrophages were analyzed for the expression and function of TG2. Macrophage-apoptotic cell interaction studies in the presence of TG2 inhibitors (both cell permeable and impermeable, irreversible and active site directed) resulted in significant inhibition of interaction indicating a possible role for TG2 in apoptotic cell clearance. Macrophage cell surface TG2 and, in particular, its cell surface crosslinking activity was found to be crucial in dictating apoptotic cell clearance. Our further studies demonstrate syndecan-4 association with TG2 and imply possible cooperation of these proteins in apoptotic cell clearance. Knockdown studies of syndecan-4 reveal its importance in apoptotic cell clearance. Our current findings suggest that TG2 has a crucial but yet to be fully defined role in apoptotic cell clearance which seems to involve protein cross linking and interaction with other cell surface receptors.
LanguageEnglish
Publication statusPublished - May 2012
EventEMBO Conference on Cellular Signaling & Molecular Medicine - Cavtat, Dubrovnik, Croatia
Duration: 25 May 201229 May 2012

Conference

ConferenceEMBO Conference on Cellular Signaling & Molecular Medicine
CountryCroatia
CityCavtat, Dubrovnik
Period25/05/1229/05/12

Fingerprint

Macrophages
Syndecan-4
transglutaminase 2
Cell Surface Receptors
Integrins
Proteins
Phagocytes
Cell Adhesion
Cell Communication
Autoimmune Diseases
Cell Movement
Monocytes
Catalytic Domain
Chronic Disease
Cell Death
Up-Regulation
Cell Count
Apoptosis

Cite this

Nadella, V., Wang, V., Griffin, M., & Devitt, A. (2012). Characterization of tissue transglutaminase 2 in macrophage function. Poster session presented at EMBO Conference on Cellular Signaling & Molecular Medicine, Cavtat, Dubrovnik, Croatia.
Nadella, Vinod ; Wang, Vivian ; Griffin, Martin ; Devitt, Andrew. / Characterization of tissue transglutaminase 2 in macrophage function. Poster session presented at EMBO Conference on Cellular Signaling & Molecular Medicine, Cavtat, Dubrovnik, Croatia.
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author = "Vinod Nadella and Vivian Wang and Martin Griffin and Andrew Devitt",
year = "2012",
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language = "English",
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Nadella, V, Wang, V, Griffin, M & Devitt, A 2012, 'Characterization of tissue transglutaminase 2 in macrophage function' EMBO Conference on Cellular Signaling & Molecular Medicine, Cavtat, Dubrovnik, Croatia, 25/05/12 - 29/05/12, .

Characterization of tissue transglutaminase 2 in macrophage function. / Nadella, Vinod; Wang, Vivian; Griffin, Martin; Devitt, Andrew.

2012. Poster session presented at EMBO Conference on Cellular Signaling & Molecular Medicine, Cavtat, Dubrovnik, Croatia.

Research output: Contribution to conferencePoster

TY - CONF

T1 - Characterization of tissue transglutaminase 2 in macrophage function

AU - Nadella, Vinod

AU - Wang, Vivian

AU - Griffin, Martin

AU - Devitt, Andrew

PY - 2012/5

Y1 - 2012/5

N2 - Programmed cell death, apoptosis, is a highly regulated process that removes damaged or unwanted cells in vivo and has significant immunological implications. Defective clearance of apoptotic cells by macrophages (professional phagocytes) is known to result in chronic inflammatory and autoimmune disease. Tissue transglutaminase 2 (TG2) is a Ca2+-dependent protein cross linking enzyme known to play an important role in a number of cell functions. Up-regulation of TG2 is thought to be involved in monocyte to macrophage differentiation and defective clearance of apoptotic cells by TG2 null mice has been described though in this context the role of TG2 is yet to be fully elucidated. Cell surface-associated TG2 is now recognized as being important in regulating cell adhesion and migration, via its association with cell surface receptors such as syndecan-4, ß1 and ß3 integrin, but its extracellular role in the clearance of apoptotic cells is still not fully explored.Our work aims to characterize the role of TG2 and its partners (e.g. syndecan-4 and ß3 integrin) in macrophage function within the framework of apoptotic cell clearance. Both THP-1 cell-derived macrophage-like cells and primary human macrophages were analyzed for the expression and function of TG2. Macrophage-apoptotic cell interaction studies in the presence of TG2 inhibitors (both cell permeable and impermeable, irreversible and active site directed) resulted in significant inhibition of interaction indicating a possible role for TG2 in apoptotic cell clearance. Macrophage cell surface TG2 and, in particular, its cell surface crosslinking activity was found to be crucial in dictating apoptotic cell clearance. Our further studies demonstrate syndecan-4 association with TG2 and imply possible cooperation of these proteins in apoptotic cell clearance. Knockdown studies of syndecan-4 reveal its importance in apoptotic cell clearance. Our current findings suggest that TG2 has a crucial but yet to be fully defined role in apoptotic cell clearance which seems to involve protein cross linking and interaction with other cell surface receptors.

AB - Programmed cell death, apoptosis, is a highly regulated process that removes damaged or unwanted cells in vivo and has significant immunological implications. Defective clearance of apoptotic cells by macrophages (professional phagocytes) is known to result in chronic inflammatory and autoimmune disease. Tissue transglutaminase 2 (TG2) is a Ca2+-dependent protein cross linking enzyme known to play an important role in a number of cell functions. Up-regulation of TG2 is thought to be involved in monocyte to macrophage differentiation and defective clearance of apoptotic cells by TG2 null mice has been described though in this context the role of TG2 is yet to be fully elucidated. Cell surface-associated TG2 is now recognized as being important in regulating cell adhesion and migration, via its association with cell surface receptors such as syndecan-4, ß1 and ß3 integrin, but its extracellular role in the clearance of apoptotic cells is still not fully explored.Our work aims to characterize the role of TG2 and its partners (e.g. syndecan-4 and ß3 integrin) in macrophage function within the framework of apoptotic cell clearance. Both THP-1 cell-derived macrophage-like cells and primary human macrophages were analyzed for the expression and function of TG2. Macrophage-apoptotic cell interaction studies in the presence of TG2 inhibitors (both cell permeable and impermeable, irreversible and active site directed) resulted in significant inhibition of interaction indicating a possible role for TG2 in apoptotic cell clearance. Macrophage cell surface TG2 and, in particular, its cell surface crosslinking activity was found to be crucial in dictating apoptotic cell clearance. Our further studies demonstrate syndecan-4 association with TG2 and imply possible cooperation of these proteins in apoptotic cell clearance. Knockdown studies of syndecan-4 reveal its importance in apoptotic cell clearance. Our current findings suggest that TG2 has a crucial but yet to be fully defined role in apoptotic cell clearance which seems to involve protein cross linking and interaction with other cell surface receptors.

M3 - Poster

ER -

Nadella V, Wang V, Griffin M, Devitt A. Characterization of tissue transglutaminase 2 in macrophage function. 2012. Poster session presented at EMBO Conference on Cellular Signaling & Molecular Medicine, Cavtat, Dubrovnik, Croatia.