Takabayshi Kenji, Corr Maripat, Hayashi Tomoko, Redecke Vanessa, Beck Lucinda, Guiney Donald, Sheppard Dean, Raz Eyal
Department of Medicine, University of California, San Diego, La Jolla, 92093, USA.
Immunity. 2006 Apr;24(4):475-87. doi: 10.1016/j.immuni.2006.02.008.
TGFbeta presented and activated by integrin alphavbeta6 expressed on alveolar epithelial cells (AEC) continuously inhibits the functionality of alveolar macrophages (AM). Despite this inhibition, AM retain their ability to respond to inhaled microorganisms. Herein we describe a homeostatic circuit through which the effects of microbial products on macrophages transiently circumvent this inhibition by repressing alphavbeta6 expression on AEC. Subsequent production of matrix metalloproteinases by activated AM activates latent TGFbeta, reinduces alphavbeta6 expression, and thereby reinstates tonic inhibition of AM function. Our results reveal how AM can be activated while minimizing their potential to inflict collateral damage to the adjacent lung tissue and indicate that tissue-specific microenvironmental factors shape organ-specific defense strategies against microbial invasion.
由肺泡上皮细胞（AEC）上表达的整合素αvβ6呈递并激活的转化生长因子β（TGFβ）持续抑制肺泡巨噬细胞（AM）的功能。尽管存在这种抑制作用，但AM仍保留对吸入微生物作出反应的能力。在此，我们描述了一种稳态回路，通过该回路，微生物产物对巨噬细胞的作用通过抑制AEC上的αvβ6表达来暂时规避这种抑制。活化的AM随后产生的基质金属蛋白酶激活潜伏的TGFβ，重新诱导αvβ6表达，从而恢复对AM功能的持续性抑制。我们的结果揭示了AM如何在激活的同时将其对相邻肺组织造成附带损害的可能性降至最低，并表明组织特异性微环境因素塑造了针对微生物入侵的器官特异性防御策略。
