RETRACTED: Induction of a homeostatic circuit in lung tissue by microbial compounds (Retracted Article. See vol 28, pg 724, 2008)

TGF beta presented and activated by integrin alpha v beta 6 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 alpha v beta 6 expression on AEC. Subsequent production of matrix metalloproteinases by activated AM activates latent TGF beta, reinduces alpha v beta 6 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.