Role of leukotriene-degrading enzymes in pulmonary response to antigen infusion in sensitized guinea pigs in vivo

To determine the role of leukotriene (LT)-degrading enzymes in allergic reactions, we studied the effects of inhibitors of gamma-glutamyl transpeptidase (gamma-GTP) and dipeptidases on increases in pulmonary insufflation pressure (PIP) and vascular permeability induced by ovalbumin (OA) antigen in guinea pigs sensitized to OA antigen in vivo. Vascular permeability was assessed by the amount of extravasated Evans blue dye from the trachea, main bronchi, and segmental bronchi. An intravenous (i.v.) administration of OA antigen (200 mu g/kg) caused increases in PIP and extravasated Evans blue dye, and OA antigen-induced effects were potentiated by gamma-GTP inhibitor L-serine berate (3 x 10(-5) M/kg, i.v.) (P < 0.05) and an inhibitor of dipeptidases, L-cysteine (3 x 10(-5) M/kg, i.v.) (P < 0.01). OA antigen-induced increases in PIP and Evans blue dye extravasation were in part inhibited by LT-receptor antagonist ONO-1078 (10(-4) M/kg, i.v.). Guinea-pig tracheal tissues contained gamma-GTP and microsomal dipeptidase activities. Histochemical and immunohistochemical studies indicate that gamma-GTP-like activity existed in the epithelium and smooth muscle, and an activity of microsomal dipeptidase was observed in the endothelial cells of microvessels and epithelium. These results suggest that LT-degrading enzymes have an important role in regulating allergic reaction in the airway in vivo.