title: The early secreted antigenic target of 6 kD of Mycobacterium tuberculosis inhibits the proliferation and differentiation of human peripheral blood CD34+cells.
abstract: Abnormalities in hematopoiesis are common in tuberculosis patients and highly prevalent in AIDS patients with tuberculosis coinfection. To explore the potential role of the early secreted antigenic target of 6-kD (ESAT-6) of Mycobacterium tuberculosis (Mtb) in abnormal hematopoiesis in tuberculosis, we studied the effect of ESAT-6 on proliferation and differentiation of in vitro-expanded CD34+cells isolated from the peripheral blood of the healthy donors. ESAT-6 but not control protein antigen 85A (Ag85A) of Mtb inhibited the proliferation of CD34+cell derived peripheral blood stem/progenitor cells (PBSPC) in a dose dependent manner when determined by MTT-assay. ESAT-6 but not Ag85A reduced the number of colony forming cells (CFC) of PBSPC by 60-90% as determined by CFC assay by incubation of CD34+cells in a semi-solid cellulose media in the presence of cytokine cocktail for two weeks. ESAT-6 but not Ag85A increased the percentages of the Annexin-V positive cells and enhanced the cleavage of caspase-3 in PBSPC in a time and dose dependent manner as determined by flow cytometry and Western blot analysis, respectively. ESAT-6 also inhibited murine bone marrow derived non-adherent cell proliferation in response to granulocyte-macrophage colony stimulating factor treatment. We conclude that ESAT-6, an essential virulence factor of Mtb, may contribute to the abnormal hematopoiesis of tuberculosis patients by inhibiting the proliferation and differentiation of hematopoietic cells via apoptosis.
authors.affiliation: The Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, 11937 US HWY 271, Tyler, TX 75708-3154, USA.
authors.forename: Na
authors.initials: N
authors.lastname: Yi
authors.affiliation: The Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, 11937 US HWY 271, Tyler, TX 75708-3154, USA.
authors.forename: Bock-Gie
authors.initials: BG
authors.lastname: Jung
authors.affiliation: The Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, 11937 US HWY 271, Tyler, TX 75708-3154, USA.
authors.forename: Xisheng
authors.initials: X
authors.lastname: Wang
authors.affiliation: The Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, 11937 US HWY 271, Tyler, TX 75708-3154, USA.
authors.forename: RamaKrishna
authors.initials: R
authors.lastname: Vankayalapati
authors.affiliation: The Department of Pulmonary Immunology, University of Texas Health Science Center at Tyler, 11937 US HWY 271, Tyler, TX 75708-3154, USA. Electronic address: buka.samten@uthct.edu.
authors.forename: Buka
authors.initials: B
authors.lastname: Samten
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D018952:Antigens, CD34 / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000378:metabolism*; D000072916:Peripheral Blood Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D000942:Antigens, Bacterial; D018952:Antigens, CD34; C000595707:BCL2 protein, human; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D019253:Proto-Oncogene Proteins c-bcl-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: CD34(+) cells; Differentiation; ESAT-6; Human; Mycobacterium tuberculosis