title: Physiological and inflammatory responses in an anthropomorphically relevant model of acute diesel exhaust particle exposure are sex and dose-dependent.
abstract: BACKGROUND
  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.
  
  
  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.
authors: Division of Clinical Sciences, Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, West Perth, WA, Australia.
authors: Catherine E
authors: CE
authors: Boylen
authors: Peter D
authors: PD
authors: Sly
authors: Graeme R
authors: GR
authors: Zosky
authors: Alexander N
authors: AN
authors: Larcombe
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002244:Carbon / Q000032:analysis; D002452:Cell Count; D018932:Chemokine CCL2 / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D052638:Particulate Matter / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D012737:Sex Factors; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D052638:Particulate Matter; D001335:Vehicle Emissions; D002244:Carbon