title: A serial immunologic and histopathologic study of lung injury induced by trimellitic anhydride.
abstract: Trimellitic anhydride (TMA) can induce immunologic lung disease in exposed workers. We have developed a rat model of TMA lung injury characterized by lung hemorrhage and an immune response to trimellityl (TM) haptenized lung proteins. The model is similar to the pulmonary disease-anemia syndrome (PDA) seen in workers exposed to TMA fumes. Sprague-Dawley rats, 15 per exposure period, inhaled micronized TMA powder, 100 micrograms/m3, 6 h/day, for 2,6, or 10 days and were sacrificed. At each time period, total, IgG, IgA, and IgM antibody to TM-rat serum albumin (TM-RSA) were measured by radiolabeled antigen binding and enzyme-linked immunosorbent assay (ELISA) in serum and bronchoalveolar lavage fluid (BAL). Hemorrhagic lung foci, weight, and displacement volume were determined, and lungs were examined by light and electron microscopy. There was no lung injury or antibody response at 2 days. There was minimal lung injury at 6 days with low levels of antibody in BAL and serum. At 10 days, there was a marked increase in hemorrhagic foci and in BAL and serum antibody levels. BAL antibody levels at 6 and 10 days had higher correlations with measures of lung injury than corresponding serum levels. There was minimal ultrastructural change at 6 days. By Day 10, there was marked intraalveolar hemorrhage, alveolar septal inflammatory nodules, abundant alveolar macrophages, and evidence of endothelial and epithelial cell injury. These results indicate that the immune response to inhaled TMA occurs parallel with the development of lung lesions, and antibody levels in BAL and serum are highly correlated with lung injury.
authors.affiliation: Department of Medicine, Northwestern University Medical School, Chicago, Illinois.
authors.forename: C R
authors.initials: CR
authors.lastname: Zeiss
authors.forename: C L
authors.initials: CL
authors.lastname: Leach
authors.forename: L J
authors.initials: LJ
authors.lastname: Smith
authors.forename: D
authors.initials: D
authors.lastname: Levitz
authors.forename: N S
authors.initials: NS
authors.lastname: Hatoum
authors.forename: P J
authors.initials: PJ
authors.lastname: Garvin
authors.forename: R
authors.initials: R
authors.lastname: Patterson
mesh_terms: D000818:Animals; D000906:Antibodies / Q000032:analysis; D000915:Antibody Affinity; D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D008297:Male; D010795:Phthalic Acids / Q000633:toxicity*; D010796:Phthalic Anhydrides / Q000276:immunology / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000906:Antibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010795:Phthalic Acids; D010796:Phthalic Anhydrides; C015559:trimellitic anhydride