| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Pathology and
Biochemistry, University of Pennsylvania School of Dental Medicine, Philadelphia, PA 19104
We have previously shown that Actinobacillus actinomycetemcomitans produces an immunosuppressive factor that is encoded by the cdtB gene, which is homologous to a family of cytolethal distending toxins (Cdt) expressed by several Gram-negative bacteria. Moreover, we have shown that CdtB impairs lymphocyte function by inducing G2 arrest of the cell cycle. We now report that both CdtB as well as an extract prepared from an Escherichia coli strain that expresses all three of the A. actinomycetemcomitans cdt genes (rCdtABC) induce apoptosis. Pretreatment of lymphocytes with either CdtB or rCdtABC leads to DNA fragmentation in activated lymphocytes at 72 and 96 h. No DNA fragmentation was induced in nonactivated cells. Flow cytometric analysis of the Cdt-treated lymphocytes demonstrates a reduction in cell size and an increase in nuclear condensation. Mitochondrial function was also perturbed in cells pretreated with either CdtB or rCdtABC. An increase in the expression of the mitochondria Ag, Apo 2.7, was observed along with evidence of the development of a mitochondrial permeability transition state; this includes a decrease in the transmembrane potential and elevated generation of reactive oxygen species. Activation of the caspase cascade, which is an important biochemical feature of the apoptotic process, was also observed in Cdt-treated lymphocytes. Overexpression of the bcl-2 gene in the human B lymphoblastoid cell line, JY, led to a decrease in Cdt-induced apoptosis. Interestingly, Bcl-2 overexpression did not block Cdt-induced G2 arrest. The implications of our results with respect to the immunosuppressive functions of Cdt proteins are discussed.
This article has been cited by other articles:
|
|
 |
|
  A. K. Azab, J. M. Runnels, C. Pitsillides, A.-S. Moreau, F. Azab, X. Leleu, X. Jia, R. Wright, B. Ospina, A. L. Carlson, et al. CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy Blood, April 30, 2009; 113(18): 4341 - 4351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Boesze-Battaglia, A. Brown, L. Walker, D. Besack, A. Zekavat, S. Wrenn, C. Krummenacher, and B. J. Shenker Cytolethal Distending Toxin-induced Cell Cycle Arrest of Lymphocytes Is Dependent upon Recognition and Binding to Cholesterol J. Biol. Chem., April 17, 2009; 284(16): 10650 - 10658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ohara, T. Hayashi, Y. Kusunoki, K. Nakachi, T. Fujiwara, H. Komatsuzawa, and M. Sugai Cytolethal Distending Toxin Induces Caspase-Dependent and -Independent Cell Death in MOLT-4 Cells Infect. Immun., October 1, 2008; 76(10): 4783 - 4791. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Handfield, H.V. Baker, and R.J. Lamont Beyond Good and Evil in the Oral Cavity: Insights into Host-Microbe Relationships Derived from Transcriptional Profiling of Gingival Cells Journal of Dental Research, March 1, 2008; 87(3): 203 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Shenker, M. Dlakic, L. P. Walker, D. Besack, E. Jaffe, E. LaBelle, and K. Boesze-Battaglia A Novel Mode of Action for a Microbial-Derived Immunotoxin: The Cytolethal Distending Toxin Subunit B Exhibits Phosphatidylinositol 3,4,5-Triphosphate Phosphatase Activity J. Immunol., April 15, 2007; 178(8): 5099 - 5108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Shenker, D. R. Demuth, and A. Zekavat Exposure of Lymphocytes to High Doses of Actinobacillus actinomycetemcomitans Cytolethal Distending Toxin Induces Rapid Onset of Apoptosis-Mediated DNA Fragmentation Infect. Immun., April 1, 2006; 74(4): 2080 - 2092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-T.A. Teng Protective and Destructive Immunity in the Periodontium: Part 2--T-cell-mediated Immunity in the Periodontium Journal of Dental Research, March 1, 2006; 85(3): 209 - 219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. Hickey, G. Majam, and P. Guerry Intracellular Survival of Campylobacter jejuni in Human Monocytic Cells and Induction of Apoptotic Death by Cytholethal Distending Toxin Infect. Immun., August 1, 2005; 73(8): 5194 - 5197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ishida, Y. Masuhiro, A. Fukushima, J. G. M. Argueta, N. Yamaguchi, S. Shiota, and S. Hanazawa Identification and Characterization of Novel Isoforms of Human DP-1: DP-1{alpha} REGULATES THE TRANSCRIPTIONAL ACTIVITY OF E2F1 AS WELL AS CELL CYCLE PROGRESSION IN A DOMINANT-NEGATIVE MANNER J. Biol. Chem., July 1, 2005; 280(26): 24642 - 24648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Ge, Y. Feng, M. T. Whary, P. R. Nambiar, S. Xu, V. Ng, N. S. Taylor, and J. G. Fox Cytolethal Distending Toxin Is Essential for Helicobacter hepaticus Colonization in Outbred Swiss Webster Mice Infect. Immun., June 1, 2005; 73(6): 3559 - 3567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Heywood, B. Henderson, and S. P Nair Cytolethal distending toxin: creating a gap in the cell cycle J. Med. Microbiol., March 1, 2005; 54(3): 207 - 216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kato, N. Sugimura, K. Nakashima, T. Nishihara, and Y. Kowashi Actinobacillus actinomycetemcomitans induces apoptosis in human monocytic THP-1 cells J. Med. Microbiol., March 1, 2005; 54(3): 293 - 298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bielaszewska, B. Sinha, T. Kuczius, and H. Karch Cytolethal Distending Toxin from Shiga Toxin-Producing Escherichia coli O157 Causes Irreversible G2/M Arrest, Inhibition of Proliferation, and Death of Human Endothelial Cells Infect. Immun., January 1, 2005; 73(1): 552 - 562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ohara, E. Oswald, and M. Sugai Cytolethal Distending Toxin: A Bacterial Bullet Targeted to Nucleus J. Biochem., October 1, 2004; 136(4): 409 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ohara, T. Hayashi, Y. Kusunoki, M. Miyauchi, T. Takata, and M. Sugai Caspase-2 and Caspase-7 Are Involved in Cytolethal Distending Toxin-Induced Apoptosis in Jurkat and MOLT-4 T-Cell Lines Infect. Immun., February 1, 2004; 72(2): 871 - 879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Shenker, D. Besack, T. McKay, L. Pankoski, A. Zekavat, and D. R. Demuth Actinobacillus actinomycetemcomitans Cytolethal Distending Toxin (Cdt): Evidence That the Holotoxin Is Composed of Three Subunits: CdtA, CdtB, and CdtC J. Immunol., January 1, 2004; 172(1): 410 - 417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Hassane, R. B. Lee, and C. L. Pickett Campylobacter jejuni Cytolethal Distending Toxin Promotes DNA Repair Responses in Normal Human Cells Infect. Immun., January 1, 2003; 71(1): 541 - 545. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. HENDERSON, M. WILSON, L. SHARP, and J. M. WARD Actinobacillus actinomycetemcomitans J. Med. Microbiol., December 1, 2002; 51(12): 1013 - 1020. [Full Text] [PDF]
|
|
|
|
|
|
L. A. Svensson, P. Henning, and T. Lagergard The Cytolethal Distending Toxin of Haemophilus ducreyi Inhibits Endothelial Cell Proliferation Infect. Immun., May 1, 2002; 70(5): 2665 - 2669. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
