title: Trimellitic anhydride-induced eosinophilia in a mouse model of occupational asthma.
abstract: Trimellitic anhydride (TMA) is a low-molecular-weight chemical known to cause occupational asthma. The present study was designed to determine if TMA elicited eosinophil infiltration into lungs of sensitized mice similar to previous studies with the protein allergen ovalbumin (OA). BALB/c mice were sensitized intradermally with 0.1 ml of 3% TMA or 0.3% OA in corn oil followed by intratracheal instillation with TMA conjugated to mouse serum albumin (TMA-MSA; 30 or 400 microg) or OA (30 microg). Nonsensitized mice received corn oil vehicle intradermally and MSA (30 microg) intratracheally. The allergic response was elicited 3 weeks later by intratracheal instillation of 30 or 400 microg TMA-MSA, OA, or control MSA. Cellular infiltration into bronchoalveolar lavage fluid (BAL) was determined 72 h later. Eosinophil peroxidase (EPO) and myeloperoxidase (MPO) activity in lung homogenates was used as an estimate of numbers of eosinophils and neutrophils, respectively, in lung tissue. In TMA-sensitized mice, TMA-MSA challenge significantly increased numbers of eosinophils in BAL and EPO in lung, indicating an increase in number of eosinophils in the airway and tissue. In nonsensitized mice, TMA-MSA challenge also caused a small but significant increase in eosinophils in BAL compared to MSA control. Total IgE in both plasma and BAL was significantly higher in TMA-sensitized compared to nonsensitized mice. The eosinophil infiltration in TMA-sensitized mice was similar in magnitude to the response in OA-sensitized mice. These studies are the first to demonstrate TMA-induced eosinophilia in mouse lung and to provide a model for comparing mechanisms and mediators responsible for the substantial eosinophilia induced by TMA and OA.
authors.affiliation: Department of Pharmacology, Toxicology Graduate Program, University of Minnesota, Duluth, MN 55812, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Regal
authors.forename: M E
authors.initials: ME
authors.lastname: Mohrman
authors.forename: D M
authors.initials: DM
authors.lastname: Sailstad
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D004195:Disease Models, Animal; D004342:Drug Hypersensitivity; D004797:Enzyme-Linked Immunosorbent Assay; D004802:Eosinophilia / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000201:enzymology; D005260:Female; D007073:Immunoglobulin E / Q000032:analysis; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D009784:Occupational Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D010796:Phthalic Anhydrides / Q000008:administration & dosage / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism; D012709:Serum Albumin / Q000008:administration & dosage
chemical_list: D000485:Allergens; D010796:Phthalic Anhydrides; D011506:Proteins; D012709:Serum Albumin; D007073:Immunoglobulin E; C015559:trimellitic anhydride