Comparison of the responses of alveolar macrophages from rats, mice and humans following particle overload [mouse]

Chromic inhalation of poorly soluble low toxicity particles, like titanium dioxide or carbon black, at high exposure levels leading to particle overload in alveolar macrophages, can induce chronic inflammation and lung cancer in rats, but not in mice. Whether this rat adverse response is predictive for humans remains unsettled for more than 40 years. In order to clarify the human relevance of the adverse rat response to particle overload, primary rat, mouse and human alveolar macrophages were exposed in vitro to overload of titanium dioxide or carbon black particles, and their activation profile was analyzed by RNAseq. We report, here, a robust transcriptomic signature of poorly soluble low toxicity particle overload in rat alveolar macrophages in vitro ,which was not observed in mouse macrophages. A similar but markedly lower response was recorded in human macrophages. Overall design: Primary mouse alveolar macrophages were exposed in vitro for 4 days to control, non-overload or overload conditions of Printex90 (carbon black) or G1-1 (titanium dioxide) particles. For each condition, three replicates were analyzed