title: Dose dependency of adjuvant activity of particulate matter from five European sites in three seasons in an ovalbumin-mouse model.
abstract: Various particulate matter (PM) samples were tested for their adjuvant potency in an animal model of allergy (ovalbumin) in the European Union study entitled Respiratory Allergy and Inflammation Due to Ambient Particles. Coarse and fine ambient particles were collected during spring, summer, and winter in Rome, Oslo, Lodz, Amsterdam, and De Zilk. De Zilk, at the Dutch seaside, has mainly westerly winds and served as a negative pollution control. EHC-93 (Ottawa dust) was used as a positive control. We studied the adjuvant potency of the particle antibody responses to ovalbumin and histopathological changes in the lung. After a sensitization phase by coexposure to EHC-93 and ovalbumin, the antibody response to ovalbumin and inflammatory responses in the lung were huge. There was more adjuvant activity in reaction to 9-mg/ml samples than to 3-mg/ml samples. A best-fit analysis of these samples shows that the ambient coarse and fine particles at these sites, in combination with allergens, have severe to mild adjuvant activity in the order Lodz, Rome, Oslo, and Amsterdam. A high dose of the fine fraction was more potent than a high dose of the coarse fraction, except at De Zilk, where the reverse was true. Spring and winter PM was more potent than summer PM. Depending on the site, either a water-soluble or a water-insoluble fraction was responsible for the adjuvant activity. A concentration of 3 mg/ml is effective for screening high-activity samples, as is a concentration of 9 mg/ml for screening low-activity samples in the ovalbumin-mouse model.
authors.affiliation: Laboratory for Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment, 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: S H
authors.initials: SH
authors.lastname: Heisterkamp
authors.forename: H
authors.initials: H
authors.lastname: van Loveren
authors.forename: F R
authors.initials: FR
authors.lastname: Cassee
mesh_terms: D000276:Adjuvants, Immunologic; D000393:Air Pollutants / Q000276:immunology* / Q000633:toxicity; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004391:Dust; D004797:Enzyme-Linked Immunosorbent Assay; D005060:Europe; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D010316:Particle Size; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000473:pathology*; D012621:Seasons; D012995:Solubility
chemical_list: D000276:Adjuvants, Immunologic; D000393:Air Pollutants; D016207:Cytokines; D004391:Dust; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin; D007770:L-Lactate Dehydrogenase