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Denis Girard - One of the best experts on this subject based on the ideXlab platform.
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activation of human neutrophils by the plant lectin viscum album agglutinin i modulation of de novo protein synthesis and evidence that caspases are involved in induction of apoptosis
Journal of Leukocyte Biology, 2000Co-Authors: Anik Savoie, Tibor Hajto, Katarina Hostanska, Valerie Lavastre, Martin Pelletier, Denis GirardAbstract:The plant lectin Viscum album agglutinin-I (VAA-I) was recently found to modulate protein synthesis and to induce apoptosis in various cells of immune origin. We found that VAA-I induces de novo protein synthesis of metabolically 35S-labeled human neutrophils when used at low concentrations ( 98% of cells at 500 and 1000 ng/mL. VAA-I was also found to reverse the delaying effect of GM-CSF on neutrophil apoptosis and to inhibit GM-CSF-induced de novo protein synthesis. In contrast to GM-CSF, VAA-I does not induce tyrosine phosphorylation by itself and does not alter the GM-CSF-induced response. Among the inhibitors used, genistein, pertussis toxin, staurosporine, H7, Calphostin C, Manoalide, BpB, quinacrine HA-1077, and z-VAD-FMK, only the latter (inhibitor of caspases-1, -3, -4, and -7) was found to inhibit VAA-I-induced neutrophil apoptosis as the percentage of apoptotic cells decrease from 98 +/- 1.3 to 54 +/- 3.2% (n=4). Furthermore, we confirm that caspases are involved in VAA-I-induced neutrophil apoptosis as we have observed the fragmentation of the cytoskeletal gelsolin protein that is known to be caspase-3-dependent. Such degradation was reversed by the z-VAD-FMK inhibitor. We conclude that induction of neutrophil apoptosis by VAA-I is a caspase-dependent mechanism that does not involve tyrosine phosphorylation events, G-proteins, PKCs, and PLA2. In addition, we conclude that at least caspase-3 is involved. Correlation between VAA-I-induced neutrophil apoptosis and VAA-I-induced inhibition of de novo protein synthesis is discussed.
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activation of human neutrophils by the plant lectin viscum album agglutinin i modulation of de novo protein synthesis and evidence that caspases are involved in induction of apoptosis
Journal of Leukocyte Biology, 2000Co-Authors: Anik Savoie, Tibor Hajto, Katarina Hostanska, Valerie Lavastre, Martin Pelletier, Denis GirardAbstract:The plant lectin Viscum album aggluti- nin-I (VAA-I) was recently found to modulate pro- tein synthesis and to induce apoptosis in various cells of immune origin. We found that VAA-I in- duces de novo protein synthesis of metabolically 35 S-labeled human neutrophils when used at low concentrations ( 98% of cells at 500 and 1000 ng/mL. VAA-I was also found to reverse the delaying effect of GM- CSF on neutrophil apoptosis and to inhibit GM- CSF-induced de novo protein synthesis. In contrast to GM-CSF, VAA-I does not induce tyrosine phos- phorylation by itself and does not alter the GM- CSF-induced response. Among the inhibitors used, genistein, pertussis toxin, staurosporine, H7, Cal- phostin C, Manoalide, BpB, quinacrine HA-1077, and z-VAD-FMK, only the latter (inhibitor of caspases-1, -3, -4, and -7) was found to inhibit VAA-I-induced neutrophil apoptosis as the per- centage of apoptotic cells decrease from 98 6 1.3 to 54 6 3.2% (n54). Furthermore, we confirm that caspases are involved in VAA-I-induced neutro- phil apoptosis as we have observed the fragmentation of the cytoskeletal gelsolin protein that is known to be caspase-3-dependent. Such degradation was reversed by the z-VAD-FMK inhibitor. We conclude that in- duction of neutrophil apoptosis by VAA-I is a caspase- dependent mechanism that does not involve tyrosine phosphorylation events, G-proteins, PKCs, and PLA 2 . In addition, we conclude that at least caspase-3 is involved. Correlation between VAA-I- induced neutrophil apoptosis and VAA-I-induced in- hibition of de novo protein synthesis is discussed. J. Leukoc. Biol. 68: 845-853; 2000.
Anik Savoie - One of the best experts on this subject based on the ideXlab platform.
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activation of human neutrophils by the plant lectin viscum album agglutinin i modulation of de novo protein synthesis and evidence that caspases are involved in induction of apoptosis
Journal of Leukocyte Biology, 2000Co-Authors: Anik Savoie, Tibor Hajto, Katarina Hostanska, Valerie Lavastre, Martin Pelletier, Denis GirardAbstract:The plant lectin Viscum album agglutinin-I (VAA-I) was recently found to modulate protein synthesis and to induce apoptosis in various cells of immune origin. We found that VAA-I induces de novo protein synthesis of metabolically 35S-labeled human neutrophils when used at low concentrations ( 98% of cells at 500 and 1000 ng/mL. VAA-I was also found to reverse the delaying effect of GM-CSF on neutrophil apoptosis and to inhibit GM-CSF-induced de novo protein synthesis. In contrast to GM-CSF, VAA-I does not induce tyrosine phosphorylation by itself and does not alter the GM-CSF-induced response. Among the inhibitors used, genistein, pertussis toxin, staurosporine, H7, Calphostin C, Manoalide, BpB, quinacrine HA-1077, and z-VAD-FMK, only the latter (inhibitor of caspases-1, -3, -4, and -7) was found to inhibit VAA-I-induced neutrophil apoptosis as the percentage of apoptotic cells decrease from 98 +/- 1.3 to 54 +/- 3.2% (n=4). Furthermore, we confirm that caspases are involved in VAA-I-induced neutrophil apoptosis as we have observed the fragmentation of the cytoskeletal gelsolin protein that is known to be caspase-3-dependent. Such degradation was reversed by the z-VAD-FMK inhibitor. We conclude that induction of neutrophil apoptosis by VAA-I is a caspase-dependent mechanism that does not involve tyrosine phosphorylation events, G-proteins, PKCs, and PLA2. In addition, we conclude that at least caspase-3 is involved. Correlation between VAA-I-induced neutrophil apoptosis and VAA-I-induced inhibition of de novo protein synthesis is discussed.
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activation of human neutrophils by the plant lectin viscum album agglutinin i modulation of de novo protein synthesis and evidence that caspases are involved in induction of apoptosis
Journal of Leukocyte Biology, 2000Co-Authors: Anik Savoie, Tibor Hajto, Katarina Hostanska, Valerie Lavastre, Martin Pelletier, Denis GirardAbstract:The plant lectin Viscum album aggluti- nin-I (VAA-I) was recently found to modulate pro- tein synthesis and to induce apoptosis in various cells of immune origin. We found that VAA-I in- duces de novo protein synthesis of metabolically 35 S-labeled human neutrophils when used at low concentrations ( 98% of cells at 500 and 1000 ng/mL. VAA-I was also found to reverse the delaying effect of GM- CSF on neutrophil apoptosis and to inhibit GM- CSF-induced de novo protein synthesis. In contrast to GM-CSF, VAA-I does not induce tyrosine phos- phorylation by itself and does not alter the GM- CSF-induced response. Among the inhibitors used, genistein, pertussis toxin, staurosporine, H7, Cal- phostin C, Manoalide, BpB, quinacrine HA-1077, and z-VAD-FMK, only the latter (inhibitor of caspases-1, -3, -4, and -7) was found to inhibit VAA-I-induced neutrophil apoptosis as the per- centage of apoptotic cells decrease from 98 6 1.3 to 54 6 3.2% (n54). Furthermore, we confirm that caspases are involved in VAA-I-induced neutro- phil apoptosis as we have observed the fragmentation of the cytoskeletal gelsolin protein that is known to be caspase-3-dependent. Such degradation was reversed by the z-VAD-FMK inhibitor. We conclude that in- duction of neutrophil apoptosis by VAA-I is a caspase- dependent mechanism that does not involve tyrosine phosphorylation events, G-proteins, PKCs, and PLA 2 . In addition, we conclude that at least caspase-3 is involved. Correlation between VAA-I- induced neutrophil apoptosis and VAA-I-induced in- hibition of de novo protein synthesis is discussed. J. Leukoc. Biol. 68: 845-853; 2000.
Miguel Payá - One of the best experts on this subject based on the ideXlab platform.
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new sesquiterpene derivatives from the sponge dysidea species with a selective inhibitor profile against human phospholipase a2 and other leukocyte functions
Journal of Natural Products, 2001Co-Authors: Clelia Giannini, Cécile Debitus, Miguel Payá, John N A Hooper, Rut Lucas, Amalia Ubeda, Maria Valeria DauriaAbstract:Two new sesquiterpene cyclopentenones, dysidenones A and B (2, 3), and a new sesquiterpene aminoquinone, dysidine (4), all containing the same rearranged drimane skeleton, have been isolated from a Dysidea sp. sponge, along with bolinaquinone (1). The structures were established from 2D NMR data. Bolinaquinone (1), dysidine (4), and a 1:1 mixture of dysidenones A and B (2, 3) significantly inhibited human synovial phospholipase A2 (PLA2) at 10 μM. Compound 4, which shows an IC50 value of 2.0 μM, exerts a higher potency and selectivity toward this enzyme than the reference inhibitor Manoalide. In addition, all of these compounds modulated at 10 μM other human leukocyte functions such as the degranulation process measured as elastase release and the superoxide production measured by chemiluminescence.
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dysidotronic acid a new and selective human phospholipase a2 inhibitor from the sponge dysidea sp
Tetrahedron Letters, 2000Co-Authors: Clelia Giannini, Inmaculada Posadas, Cécile Debitus, Miguel Payá, Maria Valeria DauriaAbstract:Abstract A new bioactive sesquiterpenoid, named dysidotronic acid 1 , with a rearranged drimane skeleton has been isolated from the sponge Dysidea sp. from Vanuatu islands, along with bolinaquinone 2 . The chemical structure of 1 was determined on the basis of spectroscopic data. Dysidotronic acid significantly inhibited human synovial phospholipase A 2 (PLA 2 ) at 10 μM, with an IC 50 value of 2.6 μM and a higher selectivity and potency towards this enzyme than the reference inhibitor Manoalide.
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effects of petrosaspongiolide m a novel phospholipase a2 inhibitor on acute and chronic inflammation
Journal of Pharmacology and Experimental Therapeutics, 1999Co-Authors: Providencia Garciapastor, Antonio Randazzo, Luigi Gomezpaloma, Maria José Alcaraz, Miguel PayáAbstract:The marine product petrosaspongiolide M is a novel inhibitor of phospholipase A2 (PLA2), showing selectivity for secretory PLA2 versus cytosolic PLA2, with a potency on the human synovial enzyme (group II) similar to that of Manoalide. This compound was more potent than Manoalide on bee venom PLA2 (group III) and had no effect on group I enzymes ( Naja naja and porcine pancreatic PLA2). Inhibition of PLA2 was also observed in vivo in the zymosan-injected rat air pouch, on the secretory enzyme accumulated in the pouch exudate. Petrosaspongiolide M decreased carrageenan paw edema in mice after the oral administration of 5, 10, or 20 mg/kg. This marine metabolite (0.01–1.0 μmol/pouch) induced a dose-dependent reduction in the levels of prostaglandin (PG)E2, leukotriene B4, and tumor necrosis factor-α in the mouse air pouch injected with zymosan 4 h after the stimulus. It also had a weaker effect on cell migration. The inflammatory response of adjuvant arthritis was reduced by petrosaspongiolide M, which also inhibited leukotriene B4 levels in serum and PGE2 levels in paw homogenates. In contrast with indomethacin, this marine compound did not reduce PGE2levels in stomach homogenates. Petrosaspongiolide M is a new inhibitor of secretory PLA2 in vitro and in vivo, with anti-inflammatory properties in acute and chronic inflammation.
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modulation of acute and chronic inflammatory processes by cacospongionolide b a novel inhibitor of human synovial phospholipase a2
British Journal of Pharmacology, 1999Co-Authors: Pablo García Pastor, Miguel Payá, Salvatore De Rosa, Alfonso De Giulio, Jose M AlcarazAbstract:Cacospongionolide B is a novel marine metabolite isolated from the sponge Fasciospongia cavernosa. In in vitro studies, this compound inhibited phospholipase A2 (PLA2), showing selectivity for secretory PLA2 (sPLA2) versus cytosolic PLA2 (cPLA2), and its potency on the human synovial enzyme (group II) was similar to that of Manoalide. This activity was confirmed in vivo in the 8 h zymosan-injected rat air pouch, on the secretory enzyme accumulating in the pouch exudate. Cacospongionolide B, that is bioavailable when is given orally, reduced the elevated levels of sPLA2 present in paw homogenates of rats with adjuvant arthritis. This marine metabolite showed topical anti-inflammatory activity on the mouse ear oedema induced by 12-O-tetradecanoylphorbol acetate (TPA) and decreased carrageenin paw oedema in mice after oral administration of 5, 10 or 20 mg kg−1. In the mouse air pouch injected with zymosan, cacospongionolide B administered into the pouch, induced a dose-dependent reduction in the levels of eicosanoids and tumour necrosis factor α (TNFα) in the exudates 4 h after the stimulus. It also had a weak effect on cell migration. The inflammatory response of adjuvant arthritis was reduced by cacospongionolide B, which did not significantly affect eicosanoid levels in serum, paw or stomach homogenates and did not induce toxic effects. Cacospongionolide B is a new inhibitor of sPLA2 in vitro and in vivo, with anti-inflammatory properties in acute and chronic inflammation. This marine metabolite was active after oral administration and able to modify TNFα levels, and may offer an interesting approach in the search for new anti-inflammatory agents. Keywords: Inflammation, phospholipase A2, rat and mouse air pouch, adjuvant arthritis, Manoalide, cacospongionolide B Introduction The activation of different phospholipases is a critical step in the biosynthesis of lipid mediators. Phospholipase A2 (PLA2) is a class of enzymes that hydrolyze the acyl group from the sn-2 position of glycerophospholipids, yielding free fatty acids and lysophospholipids. These products or their metabolites are bioactive lipids modulating different cellular processes. Mammalian cells contain diverse PLA2 which may play a distinct role in cell activation and signal transduction. Moreover, in pathologic states, increased PLA2 activity causes alteration of membrane structure and function as well as an excessive production of lipid mediators and toxic species that contributes to tissue injury. Secretory PLA2 (sPLA2, groups I, II, III and V), cytosolic PLA2 (cPLA2, group IV) and calcium-independent PLA2 have been studied (for review see Serhan et al. (1996); Dennis (1997)). Calcium-independent PLA2 is present in the myocardium and other tissues. This enzyme may regulate the incorporation of arachidonic acid into membrane phospholipids in P388D1 macrophages (Balsinde et al., 1995) and could participate in arachidonic acid release and cell spreading in murine peritoneal macrophages (Teslenko et al., 1997). It has been reported that cPLA2 play an important role in arachidonic acid release in a number of cell systems, e.g. human platelets stimulated with thrombin (Bartoli et al., 1994) or calcium ionophore (Riendeau et al., 1994), permeabilized human neutrophils (Bauldry & Wooten, 1996) or mouse peritoneal macrophages challenged with zymosan or 12-O-tetradecanoylphorbol acetate (TPA) (Qiu & Leslie, 1994). Inflammatory cytokines have been shown to induce cPLA2, resulting in high levels of eicosanoids in airway epithelial cells (Wu et al., 1997), rheumatoid synovial fibroblasts (Hulkower et al., 1994) or mouse osteoblasts (Chen et al., 1997). Group II sPLA2 can act as a signalling agent that mediates cell growth induced by interleukin-1β (IL-1β) (Wada et al., 1997). In addition, it has a role in cell activation and contributes to the inflammatory response. sPLA2 activation may participate in signal transduction events such as CD11b/CD18 (MAC-1) expression on the surface of activated human neutrophils, and adhesion or degranulation (Takasaki et al., 1996; Jacobson & Schrier, 1993). This enzyme activity secreted at inflammatory sites becomes associated with cell surfaces and hydrolyzes phospholipids, thus releasing arachidonic acid, which enters the cell and participate in the increased generation of inflammatory lipid mediators (Pfeilschifter et al., 1993; Miyake et al., 1994). In fact, administration of different types of sPLA2 can induce or amplify inflammatory responses in animals (Vishwanath et al., 1988; Tanaka et al., 1995; Cirino et al., 1994). Interestingly, inflammatory cytokines increase group II PLA2 synthesis and secretion by rheumatoid synovial fibroblasts and other cell types (Pfeilschifter et al., 1993; Bomalaski & Clark, 1993). Thus, IL-1β induces an increase in group II sPLA2 gene expression, but does not increase cPLA2 gene expression or activity, and it provokes a parallel increase in prostaglandin E2 (PGE2) production by rabbit articular chondrocytes (Jacques et al., 1997). Group II sPLA2 has been reported to release arachidonic acid in some systems and may provide the substrate for both cyclo-oxygenase (COX) and 5-lipoxygenase (5-LO) product formation in mouse bone marrow-derived mast cells (Fonteh et al., 1994). In contrast, PLA2 secreted by guinea-pig peritoneal macrophages does not participate in the synthesis of PGE2 accumulating in the media (Marshall et al., 1994). On the other hand, exocytosis of sPLA2 could modulate the activity of cPLA2 by initiating the formation of leukotriene B4 (LTB4), which after release stimulates its own receptor, thus leading to activation of cPLA2 in neutrophils (Wijkander et al., 1995). Exogenously added group I PLA2 is also believed to be involved in arachidonic acid release (Hara et al., 1991), in some cases accompanied by induction of group II PLA2, and recently a group V sPLA2 has been reported to participate in immediate prostanoid generation in the mouse macrophage cell line P388D1 (Balboa et al., 1996). Arachidonic acid mobilization can be dependent on both types of PLA2 in some systems, as in the case of delayed PGD2 generation by COX-2 in rat peritoneal macrophages stimulated by lipopolysaccharide (LPS) (Naraba et al., 1998), as well as in receptor-stimulated P388D1 macrophages (Balsinde & Dennis, 1996), and human umbilical vein endothelial cells (Murakami et al., 1993). In human monocytes stimulated by ionophore or zymosan, cPLA2 would participate preferentially in the release of arachidonic acid for prostaglandin (PG) synthesis, whereas sPLA2 probably releases the substrate for LT synthesis (Marshall et al., 1997). Marine organisms are a rich source of molecules exhibiting PLA2 inhibitory properties in vitro, mainly on secretory enzymes (for review, see Potts et al., 1992). Some of these compounds have been found to reduce experimental inflammatory responses, preferentially after topical application. We have examined the PLA2 inhibitory activity of cacospongionolide B (Figure 1), a new marine metabolite isolated from the Mediterranean sponge Fasciospongia cavernosa. The results of our studies demonstrate that cacospongionolide B is a potent inhibitor of sPLA2. We have also assessed its effects on models of acute and chronic inflammation. Figure 1 Chemical structure of cacospongionolide B. Methods sPLA2 assay sPLA2 was assayed by using a modification of the method of Franson et al. (1974). E. coli strain CECT 101 were seeded in medium containing 1% tryptone, 0.5% NaCl and 0.6% sodium dihydrogen orthophosphate, pH 5.0, and grown for 6–8 h at 37°C in the presence of 5 μCi ml−1 [3H]-oleic acid (sp. act. 10 Ci mmol−1). After centrifugation at 2500×g for 10 min, the cells were washed in buffer (0.7 M Tris-HCl, 10 mM CaCl2, 0.1% bovine serum albumin, BSA, pH 8.0), resuspended in saline and autoclaved for 30–45 min. At least 95% of the radioactivity was incorporated into phospholipids. Naja naja venom, porcine pancreatic, bee venom and human recombinant synovial enzymes were diluted in 10 μl of 100 mM Tris-HCl, 1 mM CaCl2 buffer, pH 7.5. Supernatants (10 μl) of exudates from zymosan-injected rat air pouch (Paya et al., 1996) were also used as a source of sPLA2. Enzymes were preincubated at 37°C for 5 min with 2.5 μl of test compound solution or its vehicle in a final volume of 250 μl. Incubation proceeded for 15 min in the presence of 10 μl of autoclaved oleate-labelled membranes and was terminated by addition of 100 μl ice-cold solution of 0.25% BSA in saline to a final concentration of 0.07% w/v. After centrifugation at 2500×g for 10 min at 4°C, the radioactivity in the supernatants was determined by liquid scintillation counting.
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Petrosaspongiolides M-R: New Potent and Selective Phospholipase A2 Inhibitors from the New Caledonian Marine Sponge Petrosaspongia nigra
'American Chemical Society (ACS)', 1998Co-Authors: A. Randazzo, Cécile Debitus, Miguel Payá, Maria J. Alcaraz, Luigi Minale, Garcia P. Pastor, Luigi Gomez-palomaAbstract:Five new bioactive sesterterpenes (1-5) have been isolated from the New Caledonian marine sponge Petrosaspongia nigra Bergquist and named petrosaspongiolides M-R. Their chemical structures were determined from 1D and 2D NMR studies and MS data. All compounds inhibited different preparations of phospholipase A(2) (PLA(2)) by irreversibly blocking these enzymes (particularly human synovial and bee venom, see Table 3), with IC50 values in the micromolar range. Interestingly, these compounds displayed a much lower activity (or no activity at all) toward porcine pancreas and Naja naja venom PLA(2) enzymes. The most potent compound, 1 (IC50 1.6 and 0.6 mu M for human synovial and bee venom PLA(2) enzymes, respectively), was slightly more active than Manoalide (6) (IC50 3.9 and 7.5 mu M) under our experimental conditions. Compound 3 is more selective, inhibiting-human synovial PLA(2) to a greater extent than bee venom PLA(2)
Katarina Hostanska - One of the best experts on this subject based on the ideXlab platform.
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activation of human neutrophils by the plant lectin viscum album agglutinin i modulation of de novo protein synthesis and evidence that caspases are involved in induction of apoptosis
Journal of Leukocyte Biology, 2000Co-Authors: Anik Savoie, Tibor Hajto, Katarina Hostanska, Valerie Lavastre, Martin Pelletier, Denis GirardAbstract:The plant lectin Viscum album agglutinin-I (VAA-I) was recently found to modulate protein synthesis and to induce apoptosis in various cells of immune origin. We found that VAA-I induces de novo protein synthesis of metabolically 35S-labeled human neutrophils when used at low concentrations ( 98% of cells at 500 and 1000 ng/mL. VAA-I was also found to reverse the delaying effect of GM-CSF on neutrophil apoptosis and to inhibit GM-CSF-induced de novo protein synthesis. In contrast to GM-CSF, VAA-I does not induce tyrosine phosphorylation by itself and does not alter the GM-CSF-induced response. Among the inhibitors used, genistein, pertussis toxin, staurosporine, H7, Calphostin C, Manoalide, BpB, quinacrine HA-1077, and z-VAD-FMK, only the latter (inhibitor of caspases-1, -3, -4, and -7) was found to inhibit VAA-I-induced neutrophil apoptosis as the percentage of apoptotic cells decrease from 98 +/- 1.3 to 54 +/- 3.2% (n=4). Furthermore, we confirm that caspases are involved in VAA-I-induced neutrophil apoptosis as we have observed the fragmentation of the cytoskeletal gelsolin protein that is known to be caspase-3-dependent. Such degradation was reversed by the z-VAD-FMK inhibitor. We conclude that induction of neutrophil apoptosis by VAA-I is a caspase-dependent mechanism that does not involve tyrosine phosphorylation events, G-proteins, PKCs, and PLA2. In addition, we conclude that at least caspase-3 is involved. Correlation between VAA-I-induced neutrophil apoptosis and VAA-I-induced inhibition of de novo protein synthesis is discussed.
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activation of human neutrophils by the plant lectin viscum album agglutinin i modulation of de novo protein synthesis and evidence that caspases are involved in induction of apoptosis
Journal of Leukocyte Biology, 2000Co-Authors: Anik Savoie, Tibor Hajto, Katarina Hostanska, Valerie Lavastre, Martin Pelletier, Denis GirardAbstract:The plant lectin Viscum album aggluti- nin-I (VAA-I) was recently found to modulate pro- tein synthesis and to induce apoptosis in various cells of immune origin. We found that VAA-I in- duces de novo protein synthesis of metabolically 35 S-labeled human neutrophils when used at low concentrations ( 98% of cells at 500 and 1000 ng/mL. VAA-I was also found to reverse the delaying effect of GM- CSF on neutrophil apoptosis and to inhibit GM- CSF-induced de novo protein synthesis. In contrast to GM-CSF, VAA-I does not induce tyrosine phos- phorylation by itself and does not alter the GM- CSF-induced response. Among the inhibitors used, genistein, pertussis toxin, staurosporine, H7, Cal- phostin C, Manoalide, BpB, quinacrine HA-1077, and z-VAD-FMK, only the latter (inhibitor of caspases-1, -3, -4, and -7) was found to inhibit VAA-I-induced neutrophil apoptosis as the per- centage of apoptotic cells decrease from 98 6 1.3 to 54 6 3.2% (n54). Furthermore, we confirm that caspases are involved in VAA-I-induced neutro- phil apoptosis as we have observed the fragmentation of the cytoskeletal gelsolin protein that is known to be caspase-3-dependent. Such degradation was reversed by the z-VAD-FMK inhibitor. We conclude that in- duction of neutrophil apoptosis by VAA-I is a caspase- dependent mechanism that does not involve tyrosine phosphorylation events, G-proteins, PKCs, and PLA 2 . In addition, we conclude that at least caspase-3 is involved. Correlation between VAA-I- induced neutrophil apoptosis and VAA-I-induced in- hibition of de novo protein synthesis is discussed. J. Leukoc. Biol. 68: 845-853; 2000.
Tibor Hajto - One of the best experts on this subject based on the ideXlab platform.
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activation of human neutrophils by the plant lectin viscum album agglutinin i modulation of de novo protein synthesis and evidence that caspases are involved in induction of apoptosis
Journal of Leukocyte Biology, 2000Co-Authors: Anik Savoie, Tibor Hajto, Katarina Hostanska, Valerie Lavastre, Martin Pelletier, Denis GirardAbstract:The plant lectin Viscum album agglutinin-I (VAA-I) was recently found to modulate protein synthesis and to induce apoptosis in various cells of immune origin. We found that VAA-I induces de novo protein synthesis of metabolically 35S-labeled human neutrophils when used at low concentrations ( 98% of cells at 500 and 1000 ng/mL. VAA-I was also found to reverse the delaying effect of GM-CSF on neutrophil apoptosis and to inhibit GM-CSF-induced de novo protein synthesis. In contrast to GM-CSF, VAA-I does not induce tyrosine phosphorylation by itself and does not alter the GM-CSF-induced response. Among the inhibitors used, genistein, pertussis toxin, staurosporine, H7, Calphostin C, Manoalide, BpB, quinacrine HA-1077, and z-VAD-FMK, only the latter (inhibitor of caspases-1, -3, -4, and -7) was found to inhibit VAA-I-induced neutrophil apoptosis as the percentage of apoptotic cells decrease from 98 +/- 1.3 to 54 +/- 3.2% (n=4). Furthermore, we confirm that caspases are involved in VAA-I-induced neutrophil apoptosis as we have observed the fragmentation of the cytoskeletal gelsolin protein that is known to be caspase-3-dependent. Such degradation was reversed by the z-VAD-FMK inhibitor. We conclude that induction of neutrophil apoptosis by VAA-I is a caspase-dependent mechanism that does not involve tyrosine phosphorylation events, G-proteins, PKCs, and PLA2. In addition, we conclude that at least caspase-3 is involved. Correlation between VAA-I-induced neutrophil apoptosis and VAA-I-induced inhibition of de novo protein synthesis is discussed.
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activation of human neutrophils by the plant lectin viscum album agglutinin i modulation of de novo protein synthesis and evidence that caspases are involved in induction of apoptosis
Journal of Leukocyte Biology, 2000Co-Authors: Anik Savoie, Tibor Hajto, Katarina Hostanska, Valerie Lavastre, Martin Pelletier, Denis GirardAbstract:The plant lectin Viscum album aggluti- nin-I (VAA-I) was recently found to modulate pro- tein synthesis and to induce apoptosis in various cells of immune origin. We found that VAA-I in- duces de novo protein synthesis of metabolically 35 S-labeled human neutrophils when used at low concentrations ( 98% of cells at 500 and 1000 ng/mL. VAA-I was also found to reverse the delaying effect of GM- CSF on neutrophil apoptosis and to inhibit GM- CSF-induced de novo protein synthesis. In contrast to GM-CSF, VAA-I does not induce tyrosine phos- phorylation by itself and does not alter the GM- CSF-induced response. Among the inhibitors used, genistein, pertussis toxin, staurosporine, H7, Cal- phostin C, Manoalide, BpB, quinacrine HA-1077, and z-VAD-FMK, only the latter (inhibitor of caspases-1, -3, -4, and -7) was found to inhibit VAA-I-induced neutrophil apoptosis as the per- centage of apoptotic cells decrease from 98 6 1.3 to 54 6 3.2% (n54). Furthermore, we confirm that caspases are involved in VAA-I-induced neutro- phil apoptosis as we have observed the fragmentation of the cytoskeletal gelsolin protein that is known to be caspase-3-dependent. Such degradation was reversed by the z-VAD-FMK inhibitor. We conclude that in- duction of neutrophil apoptosis by VAA-I is a caspase- dependent mechanism that does not involve tyrosine phosphorylation events, G-proteins, PKCs, and PLA 2 . In addition, we conclude that at least caspase-3 is involved. Correlation between VAA-I- induced neutrophil apoptosis and VAA-I-induced in- hibition of de novo protein synthesis is discussed. J. Leukoc. Biol. 68: 845-853; 2000.