Viscum album agglutinin-I induces apoptosis and degradation of cytoskeletal proteins via caspases in human leukaemia eosinophil AML14.3D10 cells: differences with purified human eosinophils.

Abstract

Although there are several agents that induce neutrophil apoptosis, few are known as inducers of eosinophil apoptosis. As eosinophils are potent effector cells contributing to allergic inflammation and asthma, we investigated whether the pro-apoptotic agent Viscum album agglutinin-I (VAA-I) could induce eosinophil apoptosis. VAA-I was found to induce apoptosis in eosinophilic AML14.3D10 (3D10) cells and that these cells expressed caspases-1, -2, -3, -4, -7, -8, -9 and -10. VAA-I-induced gelsolin degradation was reversed by the pan-caspase inhibitor N-benzyloxycarbonyl-V-A-D-O-methylfluoromethyl ketone (z-VAD). Also, paxillin, vimentin and lamin B1 were cleaved by caspases in VAA-I-induced 3D10 cells. VAA-I activated caspase-3 and -8 in 3D10 cells but, unlike z-VAD, treatment with a caspase-8 inhibitor slightly reversed apoptosis. Treatment of purified human eosinophils with VAA-I was found to induce apoptosis, degradation of gelsolin and lamin B1, but unlike 3D10 cells, cleavage of lamin B1 and cell apoptosis was not reversed by z-VAD. We conclude that VAA-I is a potent inducer of eosinophil apoptosis and that proteases other than those inhibited by z-VAD in 3D10 cells are involved in VAA-I-induced peripheral blood eosinophil apoptosis and lamin B1 cleavage. Thus, VAA-I represents a potential candidate for the reduction of the number of eosinophils in diseases where they play important roles.

• Authors: Valérie Lavastre, Sonia Chiasson, Hélène Cavalli, Denis Girard
• Journal: British journal of haematology (Br J Haematol) Vol. 130 Issue 4 Pg. 527-35 (Aug 2005) ISSN: 0007-1048 [Print] England
• PMID: 16098066 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytoskeletal Proteins
• Gelsolin
• LAMB1 protein, human
• Laminin
• PXN protein, human
• Paxillin
• Phosphoproteins
• Plant Preparations
• Plant Proteins
• Ribosome Inactivating Proteins, Type 2
• Toxins, Biological
• VAA-I protein, Viscum album
• Vimentin
• Ribosome Inactivating Proteins
• CASP3 protein, human
• CASP8 protein, human
• Caspase 3
• Caspase 8
• Caspases

Topics

• Acute Disease
• Apoptosis
• Caspase 3
• Caspase 8
• Caspases (analysis, metabolism)
• Cell Line, Tumor
• Cytoskeletal Proteins (analysis, drug effects, metabolism)
• DNA Fragmentation
• Eosinophils (metabolism)
• Gelsolin (analysis, metabolism)
• Humans
• Laminin (metabolism)
• Leukemia, Myeloid (metabolism)
• Paxillin
• Phosphoproteins (analysis, metabolism)
• Plant Preparations (pharmacology)
• Plant Proteins (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Ribosome Inactivating Proteins
• Ribosome Inactivating Proteins, Type 2
• Toxins, Biological (pharmacology)
• Vimentin (analysis, metabolism)