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Am. J. Respir. Crit. Care Med., Volume 161, Number 6, June 2000, 1844-1849

Effect of Eotaxin and Platelet-activating Factor on Airway Inflammation and Hyperresponsiveness in Guinea Pigs in Vivo

SATORU FUKUYAMA, HIROMASA INOUE, HISAMICHI AIZAWA,* MASAHIRO OIKE, MOTOJI KITAURA, OSAMU YOSHIE,dagger and NOBUYUKI HARA

Research Institute for Diseases of the Chest, and Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan; and Shionogi Institute for Medical Science, Osaka, Japan

Although eotaxin causes selective infiltration of eosinophils into the lung, its role in airway hyperresponsiveness remains unclear. We studied the effects of local administration of eotaxin on airway inflammation and hyperresponsiveness in guinea pigs in vivo. Airway responsiveness to inhaled histamine and differential cell counts in bronchoalveolar lavage fluid (BALF) were evaluated 12 h, 24 h, 3 d, and 7 d after intratracheal instillation of eotaxin. Significant eosinophilia in BALF was observed between 6 h and 7 d after eotaxin administration. Histologically, eosinophil accumulation was observed in the airways but not in the alveoli. In contrast, eotaxin did not affect airway responsiveness between 12 h and 7 d after its administration. We then studied the effects on airway responsiveness of subthreshold doses of interleukin 5, leukotriene D4 (LTD4), and platelet-activating factor (PAF) combined with eotaxin. Neither interleukin 5 nor LTD4 affected airway responsiveness. After eotaxin treatment, PAF significantly enhanced airway responsiveness without further increases in eosinophil counts. Eotaxin plus PAF significantly increased in eosinophil peroxidase activity in BALF compared with control and with eotaxin alone. These data indicate that eotaxin alone causes eosinophil accumulation in the airways but not hyperresponsiveness, and that additional factors such as PAF are needed to activate eosinophils for the development of airway hyperresponsiveness.




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