Content and localization of leukotriene C4 in lung tissue during biphasic allergic bronchoconstriction in the guinea pig

Abstract

Leukotriene C4 (LTC4) is a very potent bronchoconstrictor, and is believed to be an important mediator during immediate (IAR) and late asthmatic response (LAR). No direct measurement of LTC4 in lung tissue during IAR and LAR has been reported, however, and its localized site in the lung remains unclear. In an effort to clarify these issues, the content of LTC4 in lung tissue was evaluated at the onset of antigen-induced IAR and LAR, and the distribution of LTC4 was examined by immunohistochemistry. IAR and LAR were induced by inhalation of aerosolized ovalbumin (OA) in conscious guinea pigs. The development of IAR and LAR following inhaled OA exposure was determined in sensitized guinea pigs by measurement of respiratory resistance using the oscillation method. LTC4 in lung tissue was measured by radioimmunoassay at six different stages (S1: non-treated group; S2: group before OA-challenge following sensitization; S3: IAR group; S4: group two hours after IAR; S5: LAR-positive group; S6: LAR-negative group). For immunohistochemistry, non-treated guinea pigs and the sensitized animals at the onset of LAR were used. Lung sections were stained with anti-LTC4 antibody by avidin biotin peroxidase complex method (ABC method). About 70% of the guinea pigs displayed IAR, followed by LAR that peaked at 6-20 hours after OA challenge. The LTC4 content in lung tissue was significantly increased (p less than 0.01) at the onset of IAR, but was significantly decreased (p less than 0.01) after two hours, and significantly increased (p less than 0.01) at the onset of LAR.(ABSTRACT TRUNCATED AT 250 WORDS)