title: Ambient ultrafine particles provide a strong adjuvant effect in the secondary immune response: implication for traffic-related asthma flares.
abstract: We have previously demonstrated that intranasal administration of ambient ultrafine particles (UFP) acts as an adjuvant for primary allergic sensitization to ovalbumin (OVA) in Balb/c mice. It is important to find out whether inhaled UFP exert the same effect on the secondary immune response as a way of explaining asthma flares in already-sensitized individuals due to traffic exposure near a freeway. The objective of this study is to determine whether inhalation exposure to ambient UFP near an urban freeway could enhance the secondary immune response to OVA in already-sensitized mice. Prior OVA-sensitized animals were exposed to concentrated ambient UFP at the time of secondary OVA challenge in our mobile animal laboratory in Los Angeles. OVA-specific antibody production, airway morphometry, allergic airway inflammation, cytokine gene expression, and oxidative stress marker were assessed. As few as five ambient UFP exposures were sufficient to promote the OVA recall immune response, including generating allergic airway inflammation in smaller and more distal airways compared with the adjuvant effect of intranasally instilled UFP on the primary immune response. The secondary immune response was characterized by the T helper 2 and IL-17 cytokine gene expression in the lung. In summary, our results demonstrated that inhalation of prooxidative ambient UFP could effectively boost the secondary immune response to an experimental allergen, indicating that vehicular traffic exposure could exacerbate allergic inflammation in already-sensitized subjects.
authors.affiliation: Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, California 90095, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Jack R
authors.initials: JR
authors.lastname: Harkema
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Lewandowski
authors.forename: Meiying
authors.initials: M
authors.lastname: Wang
authors.forename: Lori A
authors.initials: LA
authors.lastname: Bramble
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Gookin
authors.forename: Zhi
authors.initials: Z
authors.lastname: Ning
authors.forename: Michael T
authors.initials: MT
authors.lastname: Kleinman
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sioutas
authors.forename: Andre E
authors.initials: AE
authors.lastname: Nel
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000280:Administration, Inhalation; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001249:Asthma / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006967:Hypersensitivity / Q000150:complications; D007249:Inflammation / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D052638:Particulate Matter / Q000008:administration & dosage*; D012137:Respiratory System / Q000276:immunology; D012140:Respiratory Tract Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D012720:Severity of Illness Index; D001335:Vehicle Emissions
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D052638:Particulate Matter; D001335:Vehicle Emissions; D010047:Ovalbumin