THE ROLE OF IGG1 AND IGG2 IN TRIMELLITIC ANHYDRIDE-INDUCED ALLERGIC RESPONSE IN THE GUINEA-PIG LUNG

Trimellitic anhydride (TMA) is a small molecular weight chemical used in the paint and plastics industry that can cause asthmalike 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 reac tions in this animal model; however, they also produce TMA-specific Ig G2 antibody. The purpose of the present study was to determine the rol e of IgG1 and IgG2 in the TMA-induced immediate bronchoconstriction an d delayed cellular infiltration in the guinea pig. Guinea pigs were pa ssively sensitized by intratracheal instillation of TMA-specific IgG2, an antibody preparation enriched with TMA-specific IgG1, or a combina tion of the two. The allergic response was induced by intratracheal in stillation of TMA conjugated to guinea pig serum albumin (TMA-GPSA). A significantly greater bronchoconstrictor response was observed in ani mals sensitized with a combination of the IgG2 and IgG1 preparation co mpared to those sensitized with IgG2 or the IgG1 preparation alone. Ce llular infiltration was quantified 24 h after antigen challenge by dif ferential cell counts of bronchoalveolar lavage (BAL) cells as well as by using eosinophil peroxidase (EPO) and myeloperoxidase (MPO) activi ty as a measure of the numbers of eosinophils and neutrophils, respect ively. In the BAL, passively sensitizing with IgG2 alone resulted in a n increase in both TMA-induced MPO and EPO activity. In contrast, in t he lung, passively sensitizing with a partially purified preparation o f TMA-specific IgG1 alone resulted in a significant increase in TMA-in duced EPO activity. Passively sensitizing with IgG2 in conjunction wit h the IgG1 preparation resulted in an enhanced cellular infiltration a nd lung injury over that seen with either antibody preparation alone. These data demonstrate an augmentation of IgG1-mediated responses by t he addition of IgG2 and suggest a significant role for both subclasses of IgG antibodies in this guinea pig model of TMA-induced occupationa l asthma. (C) 1998 Academic Press.