title: Surface area-dependence of gas-particle interactions influences pulmonary and neuroinflammatory outcomes.
abstract: Deleterious consequences of exposure to traffic emissions may derive from interactions between carbonaceous particulate matter (PM) and gaseous components in a manner that is dependent on the surface area or complexity of the particles. To determine the validity of this hypothesis, we examined pulmonary and neurological inflammatory outcomes in C57BL/6 and apolipoprotein E knockout (ApoE-/-) male mice after acute and chronic exposure to vehicle engine-derived particulate matter, generated as ultrafine (UFP) and fine (FP) sizes, with additional exposures using UFP or FP combined with gaseous copollutants derived from fresh gasoline and diesel emissions, labeled as UFP + G and FP + G.
  
  
  
  The UFP and UFP + G exposure groups resulted in the most profound pulmonary and neuroinflammatory effects. Phagocytosis of UFP + G particles via resident alveolar macrophages was substantial in both mouse strains, particularly after chronic exposure, with concurrent increased proinflammatory cytokine expression of CXCL1 and TNFα in the bronchial lavage fluid. In the acute exposure paradigm, only UFP and UFP + G induced significant changes in pulmonary inflammation and only in the ApoE-/-animals. Similarly, acute exposure to UFP and UFP + G increased the expression of several cytokines in the hippocampus of ApoE-/-mice including Il-1β, IL-6, Tgf-β and Tnf-α and in the hippocampus of C57BL/6 mice including Ccl5, Cxcl1, Il-1β, and Tnf-α. Interestingly, Il-6 and Tgf-β expression were decreased in the C57BL/6 hippocampus after acute exposure. Chronic exposure to UFP + G increased expression of Ccl5, Cxcl1, Il-6, and Tgf-β in the ApoE-/-hippocampus, but this effect was minimal in the C57BL/6 mice, suggesting compensatory mechanisms to manage neuroinflammation in this strain.
  
  
  
  Inflammatory responses the lung and brain were most substantial in ApoE-/-animals exposed to UFP + G, suggesting that the surface area-dependent interaction of gases and particles is an important determinant of toxic responses. As such, freshly generated UFP, in the presence of combustion-derived gas phase pollutants, may be a greater health hazard than would be predicted from PM concentration, alone, lending support for epidemiological findings of adverse neurological outcomes associated with roadway proximity.
authors.affiliation: Department of Pharmaceutical Sciences, The University of New Mexico College of Pharmacy, Albuquerque, NM, USA.
authors.forename: Christina R
authors.initials: CR
authors.lastname: Tyler
authors.affiliation: Department of Pharmaceutical Sciences, The University of New Mexico College of Pharmacy, Albuquerque, NM, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Zychowski
authors.affiliation: Department of Pharmaceutical Sciences, The University of New Mexico College of Pharmacy, Albuquerque, NM, USA.
authors.forename: Bethany N
authors.initials: BN
authors.lastname: Sanchez
authors.affiliation: Department of Pharmaceutical Sciences, The University of New Mexico College of Pharmacy, Albuquerque, NM, USA.
authors.forename: Valeria
authors.initials: V
authors.lastname: Rivero
authors.affiliation: Department of Pharmaceutical Sciences, The University of New Mexico College of Pharmacy, Albuquerque, NM, USA.
authors.forename: Selita
authors.initials: S
authors.lastname: Lucas
authors.affiliation: Department of Pharmaceutical Sciences, The University of New Mexico College of Pharmacy, Albuquerque, NM, USA.
authors.forename: Guy
authors.initials: G
authors.lastname: Herbert
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
authors.forename: June
authors.initials: J
authors.lastname: Liu
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
authors.forename: Hammad
authors.initials: H
authors.lastname: Irshad
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: McDonald
authors.affiliation: Department of Pharmacy Practice & Administrative Sciences, The University of New Mexico, Albuquerque, NM, USA.
authors.forename: Barry E
authors.initials: BE
authors.lastname: Bleske
authors.affiliation: Department of Pharmaceutical Sciences, The University of New Mexico College of Pharmacy, Albuquerque, NM, USA. MCampen@salud.unm.edu.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Campen
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000096:biosynthesis; D007249:Inflammation / Q000139:chemically induced*; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013499:Surface Properties; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D001335:Vehicle Emissions