Actin is cleaved during constitutive apoptosis

Brown, Simon; Bailey, Kevin; Savill, John

doi:10.1042/bj3230233

Cited by 133 publications

(88 citation statements)

References 46 publications

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“…To date, in human neutrophils, only the MFAP gelsolin was found to be a substrate for caspases (34). Actin is known to be cleaved during spontaneous neutrophil apoptosis, but this protein was not found to be a caspase substrate (62). Similarly, we found that the degradation of vinculin and ␣-and ␤-tubulin is not accelerated by VAA-I and that caspases do not seem to play an important role in their degradation during spontaneous apoptosis.…”

Section: Discussionsupporting

confidence: 49%

Mechanisms Involved in Spontaneous and Viscum album Agglutinin-I-Induced Human Neutrophil Apoptosis: Viscum album Agglutinin-I Accelerates the Loss of Antiapoptotic Mcl-1 Expression and the Degradation of Cytoskeletal Paxillin and Vimentin Proteins Via Caspases

Lavastre

Pelletier

Saller

et al. 2002

The Journal of Immunology

137

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Viscum album agglutinin-I (VAA-I) is a plant lectin that possesses interesting potential therapeutic properties and immunomodulatory activities. We have recently found that VAA-I is a potent inducer of human neutrophil apoptosis, but the mechanism(s) involved require further elucidation. In this study, we found that VAA-I alters mitochondrial transmembrane potential and increases intracellular levels of reactive oxygen species (ROS). Despite these observations, treatment with the mitochondrial stabilizer, bongkrekic acid, or with catalase, known to degrade H2O2, fails to reverse VAA-I-induced apoptosis. Moreover, VAA-I was found to induce apoptosis in PLB-985 cells deficient in gp91phox, indicating that the lectin acts via an ROS-independent mechanism. Pretreatment of neutrophils with brefeldin A, an inhibitor of vesicular transport, was found to reverse VAA-I-induced apoptosis. Protein expression of Mcl-1 was decreased by VAA-I. The role of caspases in the degradation of cytoskeletal proteins during both spontaneous and VAA-I-induced neutrophil apoptosis was also investigated. Paxillin and vimentin were markedly degraded by VAA-I when compared with neutrophils that undergo spontaneous apoptosis, but not vinculin or α- and β-tubulin. Caspases were involved in cytoskeletal protein degradation because preincubation with the pan-caspase inhibitor N-benzyloxycarbonyl-V-A-D-O-methylfluoromethyl ketone was found to reverse protein cleavage. We conclude that VAA-I needs to be internalized to mediate apoptosis and that its activity is not dependent on a cell surface receptor-mediated pathway. Also, we conclude that VAA-I induces apoptosis by ROS-independent and Mcl-1-dependent mechanisms and that caspases are involved in cytoskeletal protein degradation in both spontaneous and VAA-I-induced neutrophil apoptosis.

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Section: Discussionsupporting

confidence: 49%

Mechanisms Involved in Spontaneous and Viscum album Agglutinin-I-Induced Human Neutrophil Apoptosis: Viscum album Agglutinin-I Accelerates the Loss of Antiapoptotic Mcl-1 Expression and the Degradation of Cytoskeletal Paxillin and Vimentin Proteins Via Caspases

Lavastre

Pelletier

Saller

et al. 2002

The Journal of Immunology

137

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“…The possibilities that LPS may induce calpain activation and that calpain activation may regulate cytoskeletal reorganization and motility are currently under investigation. An alternative possibility is that actin cleavage is a marker of neutrophil apoptosis (52).…”

Section: Table V Analysis Of Ph 55-67 Two-dimensional Page Gelsmentioning

confidence: 99%

A Genomic and Proteomic Analysis of Activation of the Human Neutrophil by Lipopolysaccharide and Its Mediation by p38 Mitogen-activated Protein Kinase

Fessler

Malcolm

Duncan

et al. 2002

Journal of Biological Chemistry

160

133

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“…Binding of FITC-conjugated annexin V in ice-cold PBS containing calcium and magnesium as previously described (18,20) was used to assess exposure of phosphatidylserine exposure. PI was used to assess plasma membrane permeability.…”

Section: Assessment Of Pmn Morphology and Flow Cytometric Analysismentioning

confidence: 99%

Nonphlogistic Clearance of Late Apoptotic Neutrophils by Macrophages: Efficient Phagocytosis Independent of β2 Integrins

Ren

Stuart

Lindberg

et al. 2001

The Journal of Immunology

Self Cite

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Neutrophils undergo constitutive death by apoptosis, leading to safe nonphlogistic phagocytosis and clearance by macrophages. Recent work has shown that before secondary necrosis, neutrophils exhibiting classical features of apoptosis can progress to a morphologically defined late apoptotic state. However, whether such neutrophils could be safely cleared was unknown. We now report that human late apoptotic neutrophils could be purified from cultured neutrophil populations undergoing constitutive death and were subsequently ingested by human monocyte-derived macrophages by serum-independent mechanisms that did not trigger the release of IL-8 or TNF-α. Such ingestion was specifically inhibited by Abs to thrombospondin-1 and the αvβ3 vitronectin receptor. Murine bone marrow-derived macrophage phagocytosis of late and early apoptotic neutrophils occurred by similar mechanisms, proceeding with the same efficiency as that observed for wild-type controls when macrophages from αm−/− or β2−/− mice were used. We conclude that specific nonphlogistic, β2 integrin-independent mechanisms involving thrombospondin-1 and αvβ3 allow macrophages to ingest late apoptotic neutrophils without eliciting inflammatory cytokine secretion.

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Actin is cleaved during constitutive apoptosis

Cited by 133 publications

References 46 publications

Mechanisms Involved in Spontaneous and Viscum album Agglutinin-I-Induced Human Neutrophil Apoptosis: Viscum album Agglutinin-I Accelerates the Loss of Antiapoptotic Mcl-1 Expression and the Degradation of Cytoskeletal Paxillin and Vimentin Proteins Via Caspases

Mechanisms Involved in Spontaneous and Viscum album Agglutinin-I-Induced Human Neutrophil Apoptosis: Viscum album Agglutinin-I Accelerates the Loss of Antiapoptotic Mcl-1 Expression and the Degradation of Cytoskeletal Paxillin and Vimentin Proteins Via Caspases

A Genomic and Proteomic Analysis of Activation of the Human Neutrophil by Lipopolysaccharide and Its Mediation by p38 Mitogen-activated Protein Kinase

Nonphlogistic Clearance of Late Apoptotic Neutrophils by Macrophages: Efficient Phagocytosis Independent of β2 Integrins

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