Physiological and inflammatory responses in an anthropomorphically relevant model of acute diesel exhaust particle exposure are sex and dose-dependent

Context: Diesel exhaust particles (DEP) are an important contributor to suspended particulate matter (PM) in urban areas. While epidemiological evidence exists for a sex-influenced dose-response relationship between acute PM exposure and respiratory health, similar data are lacking for DEP. Further, experimental evidence showing deleterious effects on respiratory health due to acute DEP exposure is sparse. Objective: To establish and characterize a mouse model of acute DEP exposure, comparing male and female mice and assessing the kinetics of the elemental carbon content of alveolar macrophages (AMs) to relate our model to human exposure. Materials and Methods: Adult BALB/c mice were intranasally inoculated with 0 (control), 10, 30 or 100 μg DEP in saline. Bronchoalveolar lavage cellular inflammation and cytokine levels were assessed 3, 6, 12, 24, 48 and 168 hours post exposure. Elemental carbon uptake by AMs was additionally assessed at 336 and 672 hours post DEP exposure. Thoracic gas volume and lung mechanics were measured 6 and 24 hours post exposure. Results: DEP resulted in dose-dependent cellular inflammation and cytokine production in both sexes. Males and females responded differently with females having more severe and prolonged neutrophilia, monocyte chemoattractant protein-1 and developing greater abnormalities in lung function. The sexual dimorphism in response was not related to the capacity of AMs to phagocytise DEP. Conclusions: Our mouse model of acute diesel exhaust particle exposure shows a dose dependency and sexual dimorphism in response. Quantification of elemental carbon in AMs allows for comparison of the results of our study with human studies