Reactive oxygen species stimulated pulmonary epithelial cells mediate the alveolar recruitment of FasL+ killer B cells in LPS-induced acute lung injuries.

Abstract

Reactive oxygen species (ROS) are electrophilic chemical species produced from incomplete oxidation. They have long been known as aggressive molecules that lead to direct tissue and cellular damage. Recent studies have reconsidered ROS as second messengers in the initiation and amplification of cell signaling, but how ROS regulate lung tissue and immune cell remain unknown. In this study, we used a LPS-induced acute lung injury (ALI) mouse model to observe disease, progression and determine ROS-related immune responses. We found that ROS play an essential pathogenic role in ALI, however, the major role of ROS in exacerbating ALI was increasing bronchoalveolar fluid (BALF) B cells rather than eliciting tissue damage. Moreover, these pathogenic B cells are FasL+ killer B cells, which reported to damage Fas-sensitive target cells including pulmonary epithelial cells. Furthermore, via in vitro transwell assays and in vivo treatment with neutralizing antibodies. ROS promoted pulmonary epithelial cells to produce CXCL9 and CXCL10, which recruited B cells into BALF. These results demonstrated that during lung injury, instead of causing oxidative damage, ROS mainly serve as second messengers, interacting with tissue and immune cells to enhance immune responses that lead to more severe disease.