title: Adjuvant activity of ambient particulate matter of different sites, sizes, and seasons in a respiratory allergy mouse model.
abstract: In the framework of an EU project entitled, "Respiratory Allergy and Inflammation due to Ambient Particles (RAIAP)", various ambient particulate matter samples were tested for their adjuvant potency in an animal allergy model to ovalbumin. Coarse (2.5-10 microm) and fine (0.15-2.5 microm) particles were collected during the spring, summer, and winter in Rome, Oslo, Lodz, and Amsterdam. Coarse and fine particles were also collected near a seaside location in the Netherlands, where prevailing winds are westerly. These latter particles served as a control, with a minimum contribution by traffic. Ottawa dust (EHC-93) was used as a standard reference sample. Immunoglobulins (IgE, IgG1, and IgG2a), histopathological changes in the lung, cytokines, and the number of cells and their differentiation in lung lavages were used as effect parameters to study the adjuvant potency of these particles. The particles (3 mg/ml) were mixed with ovalbumin (0.4 mg/ml) and intranasally administered during the sensitization or the challenge phase. Intranasal administration of ovalbumin only induced very little antibody response, but introduced a minor inflammatory response in the lung or BAL during the sensitization and challenge phase. On the contrary, after coexposure to EHC-93 and ovalbumin, a major increase was found in immunoglobulin levels specific for ovalbumin, and a major inflammatory response in lung and BAL was induced. Coexposure to ovalbumin with 4 out of 12 collected PM samples (3 mg/ml) resulted in an increase of mainly IgE and IgG1. The histopathological changes consisted of a small to severe peribronchial and perivascular inflammatory response, a hypertrophy of bronchiolar mucous cells and an increase in eosinophils and neutrophils in the BAL. Statistical evaluation of the above-mentioned parameters showed associations with PMx (coarse and fine), site, season, season x PMx, season x site and (PMx) x site. In addition, adjuvant activity of the PMx can be ranked as Lodz > Rome = Amsterdam > Oslo. When the different seasons were compared for IgE, PM from winter was found more active compared to PM from spring and summer. Only for the histopathological lesions, statistically significant difference in effects was found between coarse and fine (coarse > fine). No associations were found between the endotoxin content and the biological effects parameters, although endotoxin was much more confined to the coarse fraction. In conclusion, PM, both coarse and fine, and from various geographic sites, was found to differ in adjuvant activity; furthermore, winter was found more active than spring and summer.
authors.affiliation: Laboratory for Toxicology, Pathology and Genetics, National Institute for Public Health and the Environment, 3720 BA Bilthoven, The Netherlands. p.steerenberg@rivm.nl
authors.forename: P A
authors.initials: PA
authors.lastname: Steerenberg
authors.forename: C E T
authors.initials: CE
authors.lastname: Withagen
authors.forename: W J
authors.initials: WJ
authors.lastname: van Dalen
authors.forename: J A M A
authors.initials: JA
authors.lastname: Dormans
authors.forename: F R
authors.initials: FR
authors.lastname: Cassee
authors.forename: S H
authors.initials: SH
authors.lastname: Heisterkamp
authors.forename: H
authors.initials: H
authors.lastname: van Loveren
mesh_terms: D000393:Air Pollutants / Q000032:analysis; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis; D004731:Endotoxins / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D007073:Immunoglobulin E / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010316:Particle Size; D012130:Respiratory Hypersensitivity / Q000473:pathology / Q000503:physiopathology*; D012621:Seasons
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D004731:Endotoxins; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin