Trimellitic anhydride-induced eosinophilia in a mouse model of occupational asthma

Trimellitic anhydride (TMA) is a low-molecular-weight chemical known to cau se occupational asthma. The present study was designed to determine if TMA elicited eosinophil infiltration into lungs of sensitized mice similar to p revious 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 follo wed by intratracheal instillation with TMA conjugated to mouse serum albumi n (TMA-MSA; 30 or 400 mug) or OA (30 mug). Nonsensitized mice received corn oil vehicle intradermally and MSA (30 mug) intratracheally. The allergic r esponse was elicited 3 weeks later by intratracheal instillation of 30 or 4 00 mug TMA-MSA, OA, or control MSA. Cellular infiltration into bronchoalveo lar lavage fluid (BAL) was determined 72 h later. Eosinophil peroxidase (EP O) and myeloperoxidase (MPO) activity in lung homogenates was used as an es timate of numbers of eosinophils and neutrophils, respectively, in lung tis sue. In TMA-sensitized mice, TMA-MSA challenge significantly increased numb ers 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 ch allenge 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 in filtration in TMA-sensitized mice was similar in magnitude to the response in OA-sensitized mice. These studies are the first to demonstrate TMA-induc ed eosinophilia in mouse lung and to provide a model for comparing mechanis ms and mediators responsible for the substantial eosinophilia induced by TM A and OA. (C) 2001 Academic Press.