In vivo PAF-induced airway eosinophil accumulation reduces bronchial responsiveness to inhaled histamine

Chronic eosinophilic bronchitis and bronchial hyperresponsiveness have been considered to be the fundamental features of bronchial asthma. However, the role of airway eosinophils in bronchial responsiveness in vivo has not been fully discussed. The aim of this study was to investigate the direct effect of airway eosinophil accumulation on bronchial responsiveness in vivo. Guinea pigs were transnasally treated with platelet activating factor (PAF) or vehicle twice a week for a total of 3 weeks. Anesthetized guinea pigs were surgically cannulated and artificially ventilated 48 h after the last administration of PAF or vehicle. Ten minutes after the installation of artificial ventilation, ascending doses of histamine were inhaled. In a subsequent study, selective inhibitors of diamine oxidase and histamine N-methyltransferase were intravenously administered before the histamine inhalation in the PAF-treated animals. Next study was conducted 20 min after treatment with indomethacin in this study line. Finally, ascending doses of methacholine were inhaled in our animal model. Proportion of eosinophils and the number of nuclear segmentation in bronchoalveolar lavage fluid significantly increased in guinea pigs treated with PAF compared with vehicle and this finding was confirmed histologically. Nevertheless, bronchial responsiveness to inhaled histamine, but not methacholine, was significantly decreased by the PAF treatment. This bronchoprotective effect induced by PAF remained following aminoguanidine and histamine N-methyltransferase administration, but abolished by treatment of indomethacin. These results suggest that in vivo airway eosinophils may reduce nonspecific bronchial responsiveness through production of inhibitory or bronchoprotective prostanoids, but not through histaminase production. (c) 2004 Elsevier Inc. All rights reserved.