GM-CSF: a double dose of protection during pneumonia.
GM-CSF: a double dose of protection during pneumonia.
复制标题
GM-CSF：肺炎期间的双倍保护剂量。
DOI：
10.1152/ajplung.00022.2012
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Quinton,LeeJ
中科院分区：
文献类型：
--
作者：
Quinton,LeeJ
INVADING MICROBES ARE RAPIDLY recognized in the lower respiratory tract, resulting in robust and often dangerous immune responses. The degree to which innate immunity is launched and maintained largely depends on gene expression programs controlled by pattern recognition receptors and transcriptional hubs such as NF-κB (8, 12). Ultimately, these signals converge to promote innate immunity and, all too often, inflammatory injury. Yet it is teleologically fitting that these same programs encode tissue-protective factors as a means to offset potentially damaging consequences of inflammation. To serve both purposes might seem contradictory, but perhaps not. In this issue, Standiford et al.(13) provide a compelling contribution to an emerging body of evidence implicating granulocyte-macrophage colony-stimulating factor (GM-CSF) as one such gene product, one protective against both infection and lung injury. GM-CSF is well appreciated for its effects on macrophage biology, surfactant homeostasis, and host defense in the lungs (15). Indeed, pharmacological blockade or genetic deletion of GM-CSF reduces multiple parameters of innate immunity in response to stimuli in the lungs, including gram-negative bacteria or LPS (1, 3). Here, the authors convincingly demonstrate that GM-CSF induction is TLR4 dependent and that it is sufficient to dramatically reduce epithelial cell death and acute lung injury in response to infection with Klebsiella pneumoniae.By as early as 6 h after the K. pneumoniae challenge, TLR4-deficient mice had significantly higher bacterial burdens in the lungs. Although this may have been expected given the genotype, the approximate 10-fold increase in air space albumin content reflects a surprisingly profound lung injury, one typically correlating with and not against inflammatory signals downstream of TLR4 and other PRRs. These data were also associated with a significant increase in epithelial apoptosis. All too often this phenotype would be dismissed simply as a consequence of increased bacterial burden, which may indeed be the truth, but perhaps not the whole truth. As importantly acknowledged by the authors, this is not the first evidence that TLR4 signaling is protective in the context of acute lung injury. For instance, others have demonstrated that TLR signaling limits injury in response to noninfectious challenges such as bleomycin (6) and hyperoxia (16). Whether and how this possibility extends to lung infections has not been adequately considered, largely because of the challenge of distinguishing between the effects of infection and immunopathology. Results from the current work by Standiford et al.(13) suggest that, during bacterial pneumonia, 1) tissue protective effects of TLR4 exist beyond its influence on antibacterial host defense and 2) GM-CSF itself may serve as an inducible effector molecule responsible for damage control.
登录
查看更多内容
影响因子：
7
作者：
Trapnell BC;Carey BC;Uchida K;Suzuki T
通讯作者：
Suzuki T
DOI：
10.1164/rccm.2009005
发表时间：
2002-07-15
影响因子：
24.7
作者：
Presneill, JJ;Harris, T;Wilson, JW
通讯作者：
Wilson, JW
影响因子：
82.9
作者：
Jiang, DH;Liang, JR;Noble, PW
通讯作者：
Noble, PW
影响因子：
8.8
作者：
Matute-Bello, G;Liles, WC;Martin, TR
通讯作者：
Martin, TR
DOI：
10.1152/ajplung.00415.2010
发表时间：
2012-03-01
影响因子：
4.9
作者：
Standiford, Louis R.;Standiford, Theodore J.;Bhan, Urvashi
通讯作者：
Bhan, Urvashi