EFFECTS OF MYCOBACTERIUM-TUBERCULOSIS ON THE BIOELECTRIC PROPERTIES OF THE ALVEOLAR EPITHELIUM

To investigate the hypothesis that Mycobacterium tuberculosis penetrat es the alveolar epithelium by down-regulating its barrier properties, we evaluated the interactions between M. tuberculosis and rat alveolar epithelial cell monolayers that are believed to share electrophysiolo gic properties of the human alveolar epithelium. Nonproteinaceous comp onents of M. tuberculosis caused marked declines in electrical resista nce and equivalent short-circuit current of the alveolar epithelial ce ll monolayers, indicating a reduction in the capacity to maintain tigh t intercellular junctions and to actively reabsorb sodium. M. tubercul osis elicited production of TNF-alpha mRNA and protein by alveolar epi thelial cells, and the effects of recombinant TNF-alpha on the bioelec tric properties of the alveolar epithelial paralleled those of M. tube rculosis. Furthermore, the effects of M. tuberculosis on alveolar epit helial resistance were abrogated by neutralizing anti-TNF-alpha antibo dies. These results indicate that M. tuberculosis elicits production o f TNF-alpha, which in turn reduces the bioelectric barrier properties of the alveolar epithelium. These findings provide insight into potent ial mechanisms by which M. tuberculosis establishes infection and dise ase in the lung.