title: The role of IgG1 and IgG2 in trimellitic anhydride-induced allergic response in the guinea pig lung.
abstract: Trimellitic anhydride (TMA) is a small molecular weight chemical used in the paint and plastics industry that can cause asthma-like symptoms in humans. Guinea pigs sensitized intradermally with TMA will respond to antigen challenge with asthma-like symptoms, including an immediate bronchoconstriction and a delayed cellular infiltration into the lung, particularly eosinophil infiltration. Sensitized guinea pigs produce TMA-specific IgG1, which is thought to be important in asthmatic reactions in this animal model; however, they also produce TMA-specific IgG2 antibody. The purpose of the present study was to determine the role of IgG1 and IgG2 in the TMA-induced immediate bronchoconstriction and delayed cellular infiltration in the guinea pig. Guinea pigs were passively sensitized by intratracheal instillation of TMA-specific IgG2, an antibody preparation enriched with TMA-specific IgG1, or a combination of the two. The allergic response was induced by intratracheal instillation of TMA conjugated to guinea pig serum albumin (TMA-GPSA). A significantly greater bronchoconstrictor response was observed in animals sensitized with a combination of the IgG2 and IgG1 preparation compared to those sensitized with IgG2 or the IgG1 preparation alone. Cellular infiltration was quantified 24 h after antigen challenge by differential cell counts of bronchoalveolar lavage (BAL) cells as well as by using eosinophil peroxidase (EPO) and myeloperoxidase (MPO) activity as a measure of the numbers of eosinophils and neutrophils, respectively. In the BAL, passively sensitizing with IgG2 alone resulted in an increase in both TMA-induced MPO and EPO activity. In contrast, in the lung, passively sensitizing with a partially purified preparation of TMA-specific IgG1 alone resulted in a significant increase in TMA-induced EPO activity. Passively sensitizing with IgG2 in conjunction with the IgG1 preparation resulted in an enhanced cellular infiltration and lung injury over that seen with either antibody preparation alone. These data demonstrate an augmentation of IgG1-mediated responses by the addition of IgG2 and suggest a significant role for both subclasses of IgG antibodies in this guinea pig model of TMA-induced occupational asthma.
authors.affiliation: Toxicology Graduate Program, University of Minnesota, Duluth 55812, USA.
authors.forename: D G
authors.initials: DG
authors.lastname: Fraser
authors.forename: F M
authors.initials: FM
authors.lastname: Graziano
authors.forename: C P
authors.initials: CP
authors.lastname: Larsen
authors.forename: J F
authors.initials: JF
authors.lastname: Regal
mesh_terms: D000368:Aged; D000485:Allergens; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016084:Bronchoconstriction / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D047209:Eosinophil Peroxidase; D004804:Eosinophils / Q000187:drug effects / Q000201:enzymology; D006168:Guinea Pigs; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology*; D007271:Injections, Intradermal; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D009195:Peroxidase / Q000032:analysis / Q000378:metabolism; D010544:Peroxidases / Q000032:analysis / Q000378:metabolism; D010796:Phthalic Anhydrides
chemical_list: D000485:Allergens; D007074:Immunoglobulin G; D010796:Phthalic Anhydrides; C015559:trimellitic anhydride; D047209:Eosinophil Peroxidase; D010544:Peroxidases; D009195:Peroxidase