| TGF-β-regulated tyrosine phosphatases induce lymphocyte apoptosis in Leishmania donovani-infected hamsters. | |
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MedLine Citation:
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PMID: 20856262 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Visceral leishmaniasis, which is caused by Leishmania donovani, is one of the major health problems of the Indian subcontinent. Infected hosts have been reported to have impaired lymphoproliferation. However, the fate of anergic cells is still elusive. In the present investigation, L. donovani-infected hamsters were used to study the mechanism of lymphocyte cell death. Lymph node-derived lymphocytes were analysed for apoptotic death through mitochondrial abnormality, caspase activity and DNA degradation. The data demonstrate that the disease progression leads to a gradual impairment of lymphocyte proliferation in the presence of Concanavalin A. The fate of the anergic lymphocytes is intrinsic apoptosis, which is evident by the depolarization of the mitochondrial membrane potential, cytosolic release of cytochrome c, caspase activation and DNA fragmentation. Tumour growth factor (TGF)-β, which is secreted by macrophages, was significantly upregulated in the lymph node compartment of infected hamsters. Adding a neutralizing TGF-β antibody and a recombinant TGF-β resulted in the downregulation and induction of lymphocyte apoptosis, respectively. Furthermore, it has been observed that TGF-β triggers the apoptotic death of lymphocytes through the upregulation of tyrosine phosphatase activity and that the use of sodium orthovanadate (Na(3)VO(4), a tyrosine phosphatase inhibitor) reduces the apoptotic frequency. Thus, this study clearly reports the novel involvement of tyrosine phosphatases in TGF-β-induced lymphocyte apoptosis in Leishmania-infected hamsters. |
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Authors:
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Rajdeep Banerjee; Sudeep Kumar; Abhik Sen; Ananda Mookerjee; Piyali Mukherjee; Syamal Roy; Subrata Pal; Pradeep Das |
Publication Detail:
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Type: Journal Article Date: 2010-09-21 |
Journal Detail:
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Title: Immunology and cell biology Volume: 89 ISSN: 1440-1711 ISO Abbreviation: Immunol. Cell Biol. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-03-17 Completed Date: 2011-08-12 Revised Date: 2011-09-02 |
Medline Journal Info:
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Nlm Unique ID: 8706300 Medline TA: Immunol Cell Biol Country: England |
Other Details:
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Languages: eng Pagination: 466-74 Citation Subset: IM |
Affiliation:
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Division of Molecular Biology, [corrected] Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, India. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Neutralizing / pharmacology Apoptosis* / drug effects Cricetinae Enzyme Inhibitors / pharmacology Female Gene Expression Regulation, Enzymologic* / immunology Leishmania donovani / immunology Leishmaniasis, Visceral / enzymology, physiopathology* Lymph Nodes / cytology, immunology Lymphocyte Activation / immunology Lymphocytes / immunology*, metabolism* Mitochondria / immunology, metabolism Protein Tyrosine Phosphatases / metabolism* Signal Transduction / drug effects, immunology Transforming Growth Factor beta* / genetics, immunology Up-Regulation / immunology Vanadates / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Neutralizing; 0/Enzyme Inhibitors; 0/Transforming Growth Factor beta; 0/Vanadates; EC 3.1.3.48/Protein Tyrosine Phosphatases |
| Comments/Corrections | |
Erratum In:
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Immunol Cell Biol. 2011 May;89(4):573 Note: Mukherjee, Piyali [added] |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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