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

Torr, Elizabeth; Gardner, David H.; Thomas, Leanne; Goodall, D.M.; Bielemeier, Anne; Willetts, Rachel; Griffiths, Helen R.; Marshall, Lindsay J.; Devitt, Andrew

doi:10.1038/cdd.2011.167

Cited by 82 publications

(87 citation statements)

References 38 publications

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“…Nucleated cells undergoing apoptosis pass through several stages, beginning with condensation of the nuclear chromatin, followed by membrane blebbing, and finally releasing EVs and apoptotic bodies [6]. However apoptotic cells are also known to release smaller vesicles (MV) in response to apoptosis induction and these MVs are known to stimulate innate immune responses [34]. Although mature human RBCs have no nucleus and organelles, however, they are able to undergo an apoptosis-like process (also called eryptosis [28,29]) with similar characteristics, e.g.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Microvesicles Released from Human Red Blood Cells

Nguyen

Wesseling

et al. 2016

Cell Physiol Biochem

101

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Background/Aims: Extracellular vesicles (EVs) are spherical fragments of cell membrane released from various cell types under physiological as well as pathological conditions. Based on their size and origin, EVs are classified as exosome, microvesicles (MVs) and apoptotic bodies. Recently, the release of MVs from human red blood cells (RBCs) under different conditions has been reported. MVs are released by outward budding and fission of the plasma membrane. However, the outward budding process itself, the release of MVs and the physical properties of these MVs have not been well investigated. The aim of this study is to investigate the formation process, isolation and characterization of MVs released from RBCs under conditions of stimulating Ca²⁺ uptake and activation of protein kinase C. Methods: Experiments were performed based on single cell fluorescence imaging, fluorescence activated cell sorter/flow cytometer (FACS), scanning electron microscopy (SEM), atomic force microscopy (AFM) and dynamic light scattering (DLS). The released MVs were collected by differential centrifugation and characterized in both their size and zeta potential. Results: Treatment of RBCs with 4-bromo-A23187 (positive control), lysophosphatidic acid (LPA), or phorbol-12 myristate-13 acetate (PMA) in the presence of 2 mM extracellular Ca²⁺ led to an alteration of cell volume and cell morphology. In stimulated RBCs, exposure of phosphatidylserine (PS) and formation of MVs were observed by using annexin V-FITC. The shedding of MVs was also observed in the case of PMA treatment in the absence of Ca²⁺, especially under the transmitted bright field illumination. By using SEM, AFM and DLS the morphology and size of stimulated RBCs, MVs were characterized. The sizes of the two populations of MVs were 205.8 ± 51.4 nm and 125.6 ± 31.4 nm, respectively. Adhesion of stimulated RBCs and MVs was observed. The zeta potential of MVs was determined in the range from - 40 mV to - 10 mV depended on the solutions and buffers used. Conclusion: An increase of intracellular Ca²⁺ or an activation of protein kinase C leads to the formation and release of MVs in human RBCs.

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Section: Introductionmentioning

confidence: 99%

Characterization of Microvesicles Released from Human Red Blood Cells

Nguyen

Wesseling

et al. 2016

Cell Physiol Biochem

101

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“…3). AC clearance by phagocytes is a multistage process and to assess the role of TG2 in the tethering of AC to MØ, TG2 inhibitors were added to MØ-AC co-cultures at 20°C, a temperature non-permissive of phagocytosis [29]. Inhibition of cell tethering was shown by all the TG2 inhibitors tested (Fig.…”

Section: Tg2 Inhibitors Reduce Mø-ac Interaction Through Actions On Mmentioning

confidence: 95%

“…Mutu l (Burkitt's lymphoma cells) were exposed to 100 mJ/cm 2 UV-B irradiation, using a Chromata-vue C71 light box and UVX radiometer (UV-P Inc., Upland, CA, USA) and incubated for 16 h to allow apoptosis to proceed [29]. For analysis of apoptotic nuclear morphology, cells were fixed in 1% (w/v) formaldehyde in PBS, stained with 4,6-diamidino-2-phenylinole (DAPI, Sigma, 250 ng/ml in PBS) for 5 min and observed using inverted epifluorescence microscopy.…”

Section: Apoptosis Induction and Quantificationmentioning

confidence: 99%

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Transglutaminase 2 interacts with syndecan-4 and CD44 at the surface of human macrophages to promote removal of apoptotic cells

Nadella

Wang

Johnson

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Tissue transglutaminase (TG2) is a multifunctional protein cross-linking enzyme that has been implicated in apoptotic cell clearance but is also important in many other cell functions including cell adhesion, migration and monocyte to macrophage differentiation. Cell surface-associated TG2 regulates cell adhesion and migration, via its association with receptors such as syndecan-4 and β1 and β3 integrins. Whilst defective apoptotic cell clearance has been described in TG2-deficient mice, the precise role of TG2 in apoptotic cell clearance remains ill-defined. Our work addresses the role of macrophage extracellular TG2 in apoptotic cell corpse clearance. Here we reveal TG2 expression and activity (cytosolic and cell surface) in human macrophages and demonstrate that inhibitors of protein crosslinking activity reduce macrophage clearance of dying cells. We show also that cell-impermeable TG2 inhibitors significantly inhibit the ability of macrophages to migrate and clear apoptotic cells through reduced macrophage recruitment to, and binding of, apoptotic cells. Association studies reveal TG2-syndecan-4 interaction through heparan sulphate side chains, and knockdown of syndecan-4 reduces cell surface TG2 activity and apoptotic cell clearance. Furthermore, inhibition of TG2 activity reduces crosslinking of CD44, reported to augment AC clearance. Thus our data define a role for TG2 activity at the surface of human macrophages in multiple stages of AC clearance and we propose that TG2, in association with heparan sulphates, may exert its effect on AC clearance via a mechanism involving the crosslinking of CD44.

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“…Gross changes in apoptotic cells include the production of plasma-membrane-bound apoptotic bodies, blebs and microvesicles (MVs), 3,4 the latter serving functions in intercellular communication, including chemoattraction and activation of phagocytes. [5][6][7][8] Taken together, these changes permit a multitude of molecular interactions with phagocytes triggering apoptotic cell engulfment and additional phagocyte responses including immunomodulation. Detailed activities of underlying receptor-ligand interactions participating in these responses remain to be defined but it is clear that interference with these processes can have pathological consequences (see, Savill et al, 9 Lauber et al, 10 Ravichandran and Lorenz, 11 Erwig and Henson, 12 Elliott and Ravichandran 13 and Gregory and Pound, 14 for reviews).…”

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confidence: 99%

Innate recognition of apoptotic cells: novel apoptotic cell-associated molecular patterns revealed by crossreactivity of anti-LPS antibodies

et al. 2013

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Cells dying by apoptosis are normally cleared by phagocytes through mechanisms that can suppress inflammation and immunity. Molecules of the innate immune system, the pattern recognition receptors (PRRs), are able to interact not only with conserved structures on microbes (pathogen-associated molecular patterns, PAMPs) but also with ligands displayed by apoptotic cells. We reasoned that PRRs might therefore interact with structures on apoptotic cells -apoptotic cell-associated molecular patterns (ACAMPs) -that are analogous to PAMPs. Here we show that certain monoclonal antibodies raised against the prototypic PAMP, lipopolysaccharide (LPS), can crossreact with apoptotic cells. We demonstrate that one such antibody interacts with a constitutively expressed intracellular protein, laminin-binding protein, which translocates to the cell surface during apoptosis and can interact with cells expressing the prototypic PRR, mCD14 as well as with CD14-negative cells. Anti-LPS cross reactive epitopes on apoptotic cells colocalised with annexin V-and C1q-binding sites on vesicular regions of apoptotic cell surfaces and were released associated with apoptotic cell-derived microvesicles (MVs). These results confirm that apoptotic cells and microbes can interact with the immune system through common elements and suggest that anti-PAMP antibodies could be used strategically to characterise novel ACAMPs associated not only with apoptotic cells but also with derived MVs.

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

Cited by 82 publications

References 38 publications

Characterization of Microvesicles Released from Human Red Blood Cells

Characterization of Microvesicles Released from Human Red Blood Cells

Transglutaminase 2 interacts with syndecan-4 and CD44 at the surface of human macrophages to promote removal of apoptotic cells

Innate recognition of apoptotic cells: novel apoptotic cell-associated molecular patterns revealed by crossreactivity of anti-LPS antibodies

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