Oberley-Deegan Rebecca E, Lee Young Min, Morey G Eli, Cook Danielle M, Chan Edward D, Crapo James D
Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
Am J Respir Cell Mol Biol. 2009 Aug;41(2):170-8. doi: 10.1165/rcmb.2008-0138OC. Epub 2008 Dec 18.
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.
脓肿分枝杆菌是一种快速生长的环境分枝杆菌，可引起严重的皮肤、软组织和肺部感染。脓肿分枝杆菌在巨噬细胞内生长，这些细胞在感染后会释放大量促炎细胞因子。金属卟啉MnTE-2-PyP是一种广泛的抗氧化剂，可减少炎症细胞信号传导。在有或没有MnTE-2-PyP的情况下，用脓肿分枝杆菌感染巨噬细胞样THP-1细胞。MnTE-2-PyP以剂量依赖性方式显著降低了感染后4天和8天从感染的THP-1细胞中回收的脓肿分枝杆菌数量。此外，当与克拉霉素联合使用时，MnTE-2-PyP可额外减少与脓肿分枝杆菌相关的细胞数量。然后阐明了MnTE-2-PyP抑制细菌生长的机制。发现MnTE-2-PyP促进了感染的THP-1细胞的存活，并增加了含有脓肿分枝杆菌的吞噬体与溶酶体的融合。
