The effect of platelet-activating factor on the responsiveness of the human nasal airway.
1. The effects of inhaled platelet-activating factor (PAF) on responsiveness of the human nasal airway were examined in normal subjects by measuring nasal airway resistance in response to histamine and bradykinin at 2, 6, 24, 48 h and 7 d after PAF administration. Eosinophil cationic protein (ECP) in nasal secretions was also measured. 2. Intranasal aerosol administration of PAF, 30 or 60 micrograms per nostril to normal human subjects induced an increased responsiveness to inhaled histamine, 50 to 400 micrograms and bradykinin, 100 micrograms per nostril at 2, 6 and 24 h following PAF treatment. However the effect was not apparent at 48 h or 7 days after PAF administration. 3. Intranasal administration of lyso-PAF, 60 micrograms by aerosol did not increase the reactivity of the nasal airway in response to histamine, 200 micrograms. 4. There was no difference in the time course of the PAF-induced hyperresponsiveness to histamine or bradykinin. 5. PAF-induced nasal hyperresponsiveness at 2 and 6 h was associated with increases in the ECP concentration of the nasal lavage fluid. 6. Vitamin E pretreatment of subjects resulted in the attenuation of the PAF-induced hyperresponsiveness to histamine, and a decrease in ECP levels of the nasal lavage fluid. 7. The results suggest that in the human nasal airway, PAF induces a non-specific hyperresponsiveness which is accompanied by eosinophil activation in the nasal cavity. Free radical production induced by PAF may contribute to the hyperresponsiveness and the activation of eosinophils.
Austin
C E
CE
Department of Pharmacology, University College London.
Foreman
J C
JC
D000280:Administration, Inhalation; D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D047091:Eosinophil Granule Proteins; D005609:Free Radicals / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D009296:Nasal Cavity / Q000187:drug effects*; D017817:Nasal Lavage Fluid / Q000166:cytology; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D012260:Ribonucleases; D014810:Vitamin E / Q000494:pharmacology
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D005609:Free Radicals; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D014810:Vitamin E; D006632:Histamine; D012260:Ribonucleases; D001920:Bradykinin