Effects of Mycobacterium tuberculosis on the bioelectric properties of the alveolar epithelium.
To investigate the hypothesis that Mycobacterium tuberculosis penetrates the alveolar epithelium by downregulating its barrier properties, we evaluated the interactions between M. tuberculosis and rat alveolar epithelial cell monolayers that are believed to share electrophysiologic properties of the human alveolar epithelium. Nonproteinaceous components of M. tuberculosis caused marked declines in electrical resistance and equivalent short-circuit current of the alveolar epithelial cell monolayers, indicating a reduction in the capacity to maintain tight intercellular junctions and to actively reabsorb sodium. M. tuberculosis elicited production of TNF-alpha mRNA and protein by alveolar epithelial cells, and the effects of recombinant TNF-alpha on the bioelectric properties of the alveolar epithelial paralleled those of M. tuberculosis. Furthermore, the effects of M. tuberculosis on alveolar epithelial resistance were abrogated by neutralizing anti-TNF-alpha antibodies. These results indicate that M. tuberculosis elicits production of TNF-alpha, which in turn reduces the bioelectric barrier properties of the alveolar epithelium. These findings provide insight into potential mechanisms by which M. tuberculosis establishes infection and disease in the lung.
Zhang
M
M
Division of Infectious Diseases, University of Southern California School of Medicine, Los Angeles 90033, USA.
Kim
K J
KJ
Iyer
D
D
Lin
Y
Y
Belisle
J
J
McEnery
K
K
Crandall
E D
ED
Barnes
P F
PF
D000818:Animals; D017097:Electric Impedance; D004848:Epithelium / Q000187:drug effects / Q000276:immunology / Q000382:microbiology / Q000502:physiology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000276:immunology / Q000382:microbiology* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha