PLATELET-ACTIVATING-FACTOR COMPROMISES AIRWAY EPITHELIAL DEFENSE FUNCTIONS

Background: The mechanism of disruption of the epithelial defense func tion observed in asthmatic airways is considered to be largely the res ult of mediators involved in allergic responses. Platelet activating f actor (PAF) might be a key mediator involved in this mechanism. Object ive: This study was designed to determine whether PAF is capable of co mpromising the epithelial defense functions, such as tight junctional barriers and the mucociliary system, Methods: A total of 120 healthy r abbits were used. Twenty of them were used as normal controls, Eighty rabbits were treated with inhalation of 10 ml of PAF (200 mu g/ml), an d 20 animals were used for the examination of epithelial defense funct ions of the trachea at 1, 10, 20, and 30 days after inhalation of PAF, Epithelial defense functions of the trachea were evaluated by ciliary activity, mucociliary transport velocity, epithelial permeability to fluorescein isothiocyanate dextrans (70,000 d), and electron microscop y of the epithelial structure. Results: PAF inhalation induced a signi ficant decrease in ciliary activity and mucociliary transport velocity , which persisted for up to 20 days. PAF inhalation also caused a sign ificant 7.4-fold increase in epithelial permeability to fluorescein is othiocyanate dextrans at 1 and 10 days. This increased epithelial perm eability returned to the normal level 20 days after PAF inhalation. Ho wever, electron microscopy-demonstrated no apparent evidence of epithe lial shedding. Conclusions: PAF-induced prolonged dysfunction of both the epithelial junctional barrier and the mucociliary system may allow enhanced entry of allergen molecules, as well as bronchoactive agonis ts to the airway parenchyma and may also significantly contribute to a n increased airway responsiveness.