A correlation between growth rate, apoptosis, and tumor necrosis factor-α in umbilical cord blood cells infected with two strains of Mycobacterium tuberculosis

• Published in: Transfusion (Philadelphia, Pa.) Vol. 49; no. 8; pp. 1720 - 1727
• Main Authors: Theus, John W., Justus, Robert S., Theus, Sue A.
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.08.2009; Wiley
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antibodies - immunology; Antibodies - pharmacology; Apoptosis - drug effects; Apoptosis - immunology; Biological and medical sciences; Blood Cells - immunology; Blood Cells - microbiology; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Line; Fetal Blood - immunology; Fetal Blood - microbiology; Humans; Medical sciences; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Mycobacterium tuberculosis - pathogenicity; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Tuberculosis - immunology; Tuberculosis - microbiology; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - pharmacology; Infection; Transfusion; Mycobacterium tuberculosis; Mycobacteriales; Cytokine; Mycobacteriaceae; Bacteria; Tumor necrosis factor β; Actinomycetes; Umbilical cord; Tumor necrosis factor α; Apoptosis
• ISSN: 0041-1132; 1537-2995
• DOI: 10.1111/j.1537-2995.2009.02187.x

BACKGROUND: Using umbilical cord blood (UCB) cells, it was demonstrated that three virulent isolates, two highly transmissible clinical isolates and the virulent laboratory strain, demonstrated rapid growth in the UCB cells, which was significantly faster than the growth rate observed for a unique isolate. There was also a significant increase in the amount of tumor necrosis factor (TNF)‐α elicited from the UCB cells after infection with the unique isolate compared to the hypervirulent isolates. This study investigated whether neutralization or addition of TNF‐α within this system would alter growth rates and apoptosis. STUDY DESIGN AND METHODS: Ten UCB samples were obtained for these experiments and adherent cells were isolated. Two clinical isolates, one virulent and one unique, were used. Colony‐forming units were assessed at 3 hours postinfection (Day 0) and on Day 7 to generate growth ratios. TNF‐α antibody or exogenous TNF‐α was added after the 3‐hour incubation period. Viability of the UCB cells was assessed. Apoptosis was measured using terminal deoxynucleotidyl transferase biotin‐dUTP nick end labeling staining. RESULTS: There was no significant difference in the growth ratio for the virulent strain regardless of the presence of TNF‐α antibody. There was a significant increase for the nonvirulent strain after the addition of antibody. There was an increase in viability for the UCB cells in the presence of antibody, suggesting a decrease in TNF‐α–dependent apoptosis. Addition of exogenous TNF‐α to the UCB cells after infection with the virulent strain decreased the growth ratio with a significant increase in apoptosis. CONCLUSIONS: The TNF‐α response of the UCB cells is related to the infecting strain and the intracellular growth of the strain of Mycobacterium tuberculosis is not directly controlled by the level of TNF‐α. This cytokine is at the start of a powerful cascade of transcription factors with numerous pleiotropic effects; consequently abrogating/enhancing a single direct outcome was difficult, with only slight alterations in growth.