Am. J. Respir. Cell Mol. Biol., Vol 15, No. 2, Aug 1996, 260-267.
Role of Leukotriene-degrading enzymes in pulmonary response to antigen infusion in sensitized guinea pigs in vivo
T Funayama, K Sekizawa, M Yamaya, K Yamauchi, I Ohno, T Ohrui, M Terajima, S Okinaga and H Sasaki
Department of Geriatric Medicine, Tohoku University School of Medicine, Sendai, Japan.
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 micrograms/kg) caused increases in PIP
and extravasated Evans blue dye, and OA antigen- induced effects were
potentiated by gamma-GTP inhibitor L-serine borate (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.
