Experimental lung injury induced by trimellitic anhydride inhalation on guinea pigs.
Trimellitic anhydride (TMA) causes lung injury by inhalation exposure in humans. In order to investigate more precisely the mechanism of lung injury by TMA, an experimental animal model of TMA-induced lung injury was established. Guinea pigs were intramuscularly injected with trimellitylated bovine serum albumin (TM BSA) with complete Freund's adjuvant (CFA). Appreciable amounts of antibodies against TM epitopes were detected in the sera of these animals. Guinea pigs that were passively sensitized with anti-TM antisera as well as the actively immunized animals developed hemorrhagic pneumonitis after TMA inhalation. It is well recognized that hyperimmune antisera of guinea pigs contain two subclasses of IgG antibodies, IgG1 and IgG2, which are known as homocytotropic and heterocytotropic antibodies, respectively. To determine the role of these antibodies in the airway injury with alveolar hemorrhages, they were isolated by gel filtration and by ion exchange column chromatography, and the guinea pigs that were sensitized with each of these antibodies were exposed to TMA inhalation. The extent of lung injury in these animals was quantitatively determined by the measurements of lung extravasation of Evans blue dye injected intravenously after TMA inhalation. Significant increases in the extravasation of dye were observed in both animal groups sensitized with IgG1 and IgG2 antibodies. In addition, results obtained with heat-treated antisera and IgG1 antibody did not significantly differ from those obtained with untreated samples. These results suggest that the lung injury resulting from TMA inhalation exposure can be induced with humoral antibodies, not only IgG1 but also IgG2, and that at least two types of allergic reactions are involved in the pathogenesis of lung injury.
Tao
Y
Y
Department of Immunology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Sugiura
T
T
Nakamura
H
H
Kido
M
M
Tanaka
I
I
Kuroiwa
A
A
D000542:Alveolitis, Extrinsic Allergic / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D000818:Animals; D000906:Antibodies / Q000302:isolation & purification; D000917:Antibody Formation / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D006470:Hemorrhage / Q000139:chemically induced; D007114:Immunization; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000302:isolation & purification; D010796:Phthalic Anhydrides / Q000276:immunology / Q000633:toxicity*
D000906:Antibodies; D007074:Immunoglobulin G; D010796:Phthalic Anhydrides; C015559:trimellitic anhydride