Differential transcriptional responses of murine alveolar macrophages to elongated mineral particles of asbestiform and non-asbestiform varieties

Occupational exposures to asbestiform elongated mineral particles (EMPs) may lead to diffuse fibrosis, lung cancer, malignant mesothelioma and autoimmune diseases. Cleavage fragments (CF) are chemically identical to asbestiform varieties of parent mineral, but there is no consensus on whether to treat them as asbestos from toxicological and regulatory standpoints. Alveolar macrophages (AM) are the first-responders to inhaled particulates, participating in clearance, and activating the other resident and recruited immunocompetent cells, which has an impact on the long-term outcomes. In the current study we addressed the question of how asbestiform vs. non-asbestiform EMPs affect AM responses. Max Planck Institute (MPI) cells, a non-transformed mouse line that has AM phenotype and genotype, were treated with surface area-equivalent concentrations of respirable asbestiform and non-asbestiform riebeckite/tremolite EMPs for 24h. Detectable changes in macrophage gene expression happen within 6-24 hours post-stimuli (Schneider et al., 2019), thus we performed the next generation RNA sequencing of the MPI cells 24 hours post exposure to surface area-equivalent doses of riebeckite and tremolite EMPs to see if AM immediate transcriptional reprogramming patterns are intrinsic for different minerals and/or crystallization habit. Global RNA expression profiles of the Max Planck Institute (MPI) cells 24 hours after treatment mith various elongated mineral particles (n=3 per treament type), were compared with expression profiles of untreated cells (n=3).