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 allergi c reactions, we studied the effects of inhibitors of gamma-glutamyl tr anspeptidase (gamma-GTP) and dipeptidases on increases in pulmonary in sufflation pressure (PIP) and vascular permeability induced by ovalbum in (OA) antigen in guinea pigs sensitized to OA antigen in vivo. Vascu lar permeability was assessed by the amount of extravasated Evans blue dye from the trachea, main bronchi, and segmental bronchi. An intrave nous (i.v.) administration of OA antigen (200 mu g/kg) caused increase s in PIP and extravasated Evans blue dye, and OA antigen-induced effec ts 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-recepto r antagonist ONO-1078 (10(-4) M/kg, i.v.). Guinea-pig tracheal tissues contained gamma-GTP and microsomal dipeptidase activities. Histochemi cal and immunohistochemical studies indicate that gamma-GTP-like activ ity existed in the epithelium and smooth muscle, and an activity of mi crosomal dipeptidase was observed in the endothelial cells of microves sels and epithelium. These results suggest that LT-degrading enzymes h ave an important role in regulating allergic reaction in the airway in vivo.