Induction of apoptosis/necrosis in various human cell lineages by Haemophilus ducreyi cytolethal distending toxin

We investigated the impact of highly purified Haemophilus ducreyi cytolethal distending toxin (HdCDT) on the apoptosis and necrosis of various human cells; including myeloid cells, epithelial cells, keratinocytes, and primary fibroblasts. The levels of apoptosis and necrosis induced in these cells w...

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Bibliographic Details
Published in:	Toxicon (Oxford) Vol. 45; no. 6; pp. 767 - 776
Main Authors:	Wising, Catharina, Azem, Jozef, Zetterberg, Madeleine, Svensson, Liselott A., Ahlman, Karin, Lagergård, Teresa
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 01-05-2005 Elsevier Science
Subjects:	Annexin A5 Apoptosis Apoptosis - drug effects Bacterial Toxins Bacterial Toxins - toxicity Bacteriology Biological and medical sciences Caspase 3 Caspases Caspases - metabolism Cell Line Cell Line, Tumor chemistry Cytolethal distending toxin Dose-Response Relationship Dose-Response Relationship, Drug Drug drug effects Epithelial Cells Epithelial Cells - drug effects Fibroblasts Fibroblasts - drug effects Flow Cytometry Fundamental and applied biological sciences. Psychology Haemophilus ducreyi Haemophilus ducreyi - chemistry Humans Keratinocytes Keratinocytes - drug effects MEDICAL AND HEALTH SCIENCES MEDICIN OCH HÄLSOVETENSKAP metabolism Microbiology Myeloid Cells Myeloid Cells - drug effects Necrosis Nonparametric Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains Phosphatidylserines Phosphatidylserines - metabolism Propidium Protein Transport Protein Transport - drug effects Statistics Statistics, Nonparametric toxicity Tumor Cytolethal distending toxin Haemophilus ducreyi Apoptosis Necrosis Pasteurellaceae Human Toxin Cell death Toxicity Bacteria In vitro
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Summary:	We investigated the impact of highly purified Haemophilus ducreyi cytolethal distending toxin (HdCDT) on the apoptosis and necrosis of various human cells; including myeloid cells, epithelial cells, keratinocytes, and primary fibroblasts. The levels of apoptosis and necrosis induced in these cells were compared to those induced by HdCDT in human T cells and in the Jurkat T cell line. Levels of caspase-3 activity were measured, and membrane changes like phosphatidylserine (PS) translocation was evaluated after double-staining with the fluorescein isothiocyanate (FITC)-labeled annexin V and propidium iodide (PI) using flow cytometry. HdCDT induced various degrees of apoptosis and necrosis in dose- and time-dependent manners in cells of various lineages. Early and late apoptosis (annexin V-stained cells) were induced in more than 90% of T cells and monocytes after treatment with 100 ng/ml HdCDT for 24 and 48 h, respectively. The corresponding numbers for epithelial cells, keratinocytes, and fibroblasts were 26–32% after treatment with 100 ng/ml HdCDT for 48 h. HdCDT appears to eliminate effectively by inducing apoptosis those cells that are involved in immune responses. Epithelial cells, keratinocytes and fibroblasts, which are important for the healing of chancroid ulcers, are eliminated by apoptosis or necrosis after contact with HdCDT, albeit slower and to a lesser extent than T cells.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0041-0101 1879-3150
DOI:	10.1016/j.toxicon.2005.01.016