ARS | Publication request: APOPTOTIC CELL DEATH IN GRANULOMAS USING A SWINE MODEL OF TUBERCULOSIS AND OPIATE ADDICTION

Submitted to: Keystone Symposium Tb Molecular Mechanisms and Immunologic Aspects
Publication Type: Abstract Only
Publication Acceptance Date: April 2, 1998
Publication Date: N/A

Technical Abstract: The prevalence of tuberculosis in the United States is increasing among IV drug users. Central to the pathogenesis of tuberculosis is the survival of mycobacteria within macrophages. Conversely, key to the control of infection is adequate cell-mediated immunity. Virulent Mycobacterium tuberculosis and the avirulent M. bovis BCG have been shown to induce apoptotic cell death in human macrophages in vitro. Additionally, opiates have been shown to impair macrophage and T-cell function. To examine the role of apoptosis in tuberculous granulomas and the differential effects of opiates on apoptosis we used a swine model of tuberculosis and opiate toxicity, using morphine alkaloid and virulent M. bovis. Pigs were euthanatized and examined on days 30 or 45 after inoculation. Specimens of tracheobronchial, mediastinal, and hepatic lymph node were processed for light microscopy and by the Tdt-mediated dUTP nick end labeling (TUNEL) method to detect apoptotic cells. Granuloma morphology and lesion severit were similar between treatment groups. Similarly, regardless of M. bovis dosage or morphine administration, TUNEL was located in macrophages surrounding necrotic foci, as well as in lymphocytes peripheral to the macrophage rich zone of the granuloma. We conclude that apoptotic cell death does occur in macrophages and lymphocytes in vivo within M. bovis-induced granulomas. However, within the parameters of this study, dosage of M. bovis or morphine administration did not influence the level of apoptotic cell death.