Platelet activating factor compromises airway epithelial defense functions.
BACKGROUND
The mechanism of disruption of the epithelial defense function observed in asthmatic airways is considered to be largely the result of mediators involved in allergic responses. Platelet activating factor (PAF) might be a key mediator involved in this mechanism.


OBJECTIVE
This study was designed to determine whether PAF is capable of compromising the epithelial defense functions, such as tight junctional barriers and the mucociliary system.


METHODS
A total of 120 healthy rabbits were used. Twenty of them were used as normal controls. Eighty rabbits were treated with inhalation of 10 ml of PAF (200 microg/ml), and 20 animals were used for the examination of epithelial defense functions 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 microscopy of the epithelial structure.


RESULTS
PAF inhalation induced a significant decrease in ciliary activity and mucociliary transport velocity, which persisted for up to 20 days. PAF inhalation also caused a significant 7.4-fold increase in epithelial permeability to fluorescein isothiocyanate dextrans at I and 10 days. This increased epithelial permeability returned to the normal level 20 days after PAF inhalation. However, electron microscopy demonstrated no apparent evidence of epithelial 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 agonists to the airway parenchyma and may also significantly contribute to an increased airway responsiveness.
Ohashi
Y
Y
Department of Otolaryngology, Osaka City University Medical School, Osaka, Japan.
Nakai
Y
Y
Morimoto
K
K
Tanaka
A
A
Kakinoki
Y
Y
Ohno
Y
Y
Masamoto
T
T
Kato
A
A
D000280:Administration, Inhalation; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002923:Cilia / Q000187:drug effects / Q000502:physiology; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000494:pharmacology*; D009079:Mucociliary Clearance / Q000187:drug effects / Q000502:physiology; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000494:pharmacology*; D011817:Rabbits; D014132:Trachea / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*
D018836:Inflammation Mediators; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor