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

Savoie, Anik; Lavastre, Valérie; Pelletier, Martin; Hajto, Tibor; Hostanska, Katarina et Girard, Denis ORCID: https://orcid.org/0000-0002-3342-5027 (2000). 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 , vol. 68 , nº 6. pp. 845-853. DOI: 10.1189/jlb.68.6.845.

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Résumé

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 (< 100 ng/mL) but acts as an inhibitor at higher concentrations. Using both flow cytometry (FITC-Annexin-V/PI labeling) and cytology (Diff-Quick staining) approaches, we found that VAA-I could not modulate neutrophil apoptosis at low concentrations but could induce it in >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.

Type de document:	Article
Mots-clés libres:	Signal transduction inhibitors; cytology; flow cytometry; gelsolin
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	14 avr. 2025 15:40
Dernière modification:	14 avr. 2025 15:40
URI:	https://espace.inrs.ca/id/eprint/15157

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