title: Adjuvant activity of ambient particulate matter in macrophage activity-suppressed, N-acetylcysteine-treated, iNOS- and IL-4-deficient mice.
abstract: In previous studies, we have shown strong adjuvant activity for Ottawa dust (EHC-93) after coexposure of the BALB/c mouse to EHC-93 and ovalbumin. Mice were intranasally sensitized at days 0 and 14 with 200 microg ovalbumin and 150 microg EHC-93, and challenged with ovalbumin at days 35, 38, and 41 with 200 microg ovalbumin. Mice were autopsied at day 42. This adjuvant activity was shown for the antibody response to ovalbumin (immunoglobulins E, G1, and G2a), histopathological lesions in the lung, cytokines, and the numbers of eosinophils in lung lavages. To study the mechanisms of this adjuvant activity, mice (BALB/cC.D2-Vil6) with natural-resistance-associated macrophage protein (Nramp1s), BALB/c mice pretreated with the antioxidant N-acetylcysteine (NAC), mice (B6.129P2-Nos2tmLau) deficient in inducible nitric oxide synthase (iNOS), and mice with interleukin-4 (IL-4) deficiency (BALB/cIl4< tm2Nnt) were coexposed to ovalbumin and EHC-93. Our studies have shown that the adjuvant activity induced after such coexposure does not change if the macrophage activation of the mice is disturbed or if the mice have been pretreated with N-acetylcysteine. In addition, the adjuvant activity does not develop through the pathway in which inducible nitric oxide synthase is involved. Because the histopathological lesions are statistically significant less in the IL-4 knockout strain in comparison with the wild type, we conclude that interleukin-4 might play an important role in the adjuvant activity caused by EHC-93.
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: H
authors.initials: H
authors.lastname: van Loveren
mesh_terms: D000111:Acetylcysteine / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000281:Administration, Intranasal; D000393:Air Pollutants / Q000032:analysis / Q000276:immunology; D000818:Animals; D027682:Cation Transport Proteins / Q000276:immunology / Q000378:metabolism; D004391:Dust / Q000032:analysis / Q000276:immunology; D015847:Interleukin-4 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout / Q000235:genetics*; D009426:Netherlands; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D052247:Nitric Oxide Synthase Type II; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D010316:Particle Size; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis / Q000276:immunology; D013997:Time Factors; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D000111:Acetylcysteine; D000276:Adjuvants, Immunologic; D000393:Air Pollutants; D027682:Cation Transport Proteins; D004391:Dust; D015847:Interleukin-4; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D010047:Ovalbumin; D011084:Polycyclic Aromatic Hydrocarbons; D000099173:Natural Resistance-associated Macrophage Protein 1; C496317:Nos2 protein, mouse