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Published ahead of print on December 18, 2008, doi:10.1165/rcmb.2008-0138OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 41, pp. 170-178, 2009
© 2009 American Thoracic Society
DOI: 10.1165/rcmb.2008-0138OC

The Antioxidant Mimetic, MnTE-2-PyP, Reduces Intracellular Growth of Mycobacterium abscessus

Rebecca E. Oberley-Deegan1, Young Min Lee1,2, G. Eli Morey1, Danielle M. Cook1, Edward D. Chan1 and James D. Crapo1

1 Department of Medicine, National Jewish Health, Denver, Colorado; and 2 Department of Medicine, Pusan Paik Hospital, College of Medicine, Inje University, Busan, Korea

Correspondence and requests for reprints should be addressed to Rebecca E. Oberley-Deegan, Ph.D., Department of Medicine, National Jewish Health, Denver, CO 80206. E-mail: oberleyr{at}njc.org

Mycobacterium abscessus is a rapidly growing environmental mycobacterium that can cause severe skin, soft tissue, and lung infections. M. abscessus grows inside macrophages, and these cells release a vast number of proinflammatory cytokines in response to infections. The metalloporphyrin, MnTE-2-PyP, is a broad antioxidant that reduces inflammatory cell signaling. Macrophage-like THP-1 cells were infected with M. abscessus in the presence or absence of MnTE-2-PyP. MnTE-2-PyP significantly decreased, in a dose-dependent manner, the number of M. abscessus organisms recovered from infected THP-1 cells 4 and 8 days after infection. Furthermore, when combined with clarithromycin, MnTE-2-PyP additively reduced the number of cells associated with M. abscessus. A mechanism of bacterial growth inhibition by MnTE-2-PyP was then elucidated. It was found that MnTE-2-PyP promoted the survival of infected THP-1 cells and increased fusion of M. abscessus–containing phagosomes with lysosomes.

Key Words: antioxidant mimetic • MnTE-2-PyP • Mycobacterium abscessus • THP-1 cells


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