85 Role of extracellular vesicles in nanoparticle-induced lung inflammation

Abstract Inhalation of nanoparticles (NPs) frequently elicits a pro-inflammatory response of the lung, characterized by the influx of neutrophilic granulocytes into the airspace. Recently extracellular vesicles (EVs) released under pathophysiologic conditions from alveolar cells, have been shown to contribute to the pulmonary inflammatory response. Previously, we found that the application of a membrane stabilizer (cromolyn) into mouse lungs, significantly and persistently attenuated neutrophil influx from pulmonary microvessels after carboxyl-modified quantum dot NP (cQD-NPs) as well as carbon black NP (CNP) inhalation (Liu et al. Sci. Adv. 2025). Likewise, pretreatment of mice with GW4869 an inhibitor of exosome biogenesis/release diminished the NP induced inflammatory response. The transfer of EVs obtained from the bronchoalveolar lavage fluid (BALF) of mice after 90 min of NP exposure to healthy mice resulted in rapid neutrophilia, as determined by intravital lung microscopy, whereas EVs from control mice did not induce inflammation in the recipients. To identify the cellular origin and molecular mechanisms of EV-induced neutrophilia in the lungs of mice, we are currently performing time-resolved proteome analyses of EV samples. Taken together we have strong indications that EVs, released in the alveolar region, are involved in the initiation of neutrophilic immune response after NP inhalation.