PAF-induced airways hyperreactivity is modulated by mast cells in mice.
We tested the hypothesis that mast cells contribute to platelet-activating factor (PAF)-induced airways hyperreactivity and hyperpermeability in mice. Airways reactivity to acetylcholine (ACh) and lung permeability to Evans blue (EB) dye were measured before and after PAF challenge in genetically mast cell-deficient (WBB6F1 W/Wv) and normal congenic (WBB6F1 +/+) mice, as well as mast cell-reconstituted (BMT W/Wv) mice. In addition, prostaglandin D2 (PGD2), a mast cell-specific mediator, was measured in the bronchoalveolar lavage (BAL) from +/+ and W/Wv mice to determine if lung mast cell activation was a consequence of PAF challenge. Genetically PAF-sensitive AKR/J mice were also treated with the mast cell stabilizer nedocromil prior to assessment of PAF effects on ACh reactivity. Intravenous PAF (10 micrograms/kg) induced a significant (P < 0.05) increase in airways reactivity to ACh (25 micrograms/kg) in both +/+ (371 +/- 52%) and W/Wv (122 +/- 24%) mice. There was a significantly greater increase in +/+ compared with W/Wv mice. PAF-induced hyperreactivity to ACh in BMT W/Wv mice (191 +/- 44%) was significantly (P < 0.05) greater than age-matched W/Wv mice (80 +/- 16%), but not significantly different from age-matched +/+ mice (153 +/- 44%). PAF (10 micrograms/kg) also significantly (P < 0.5) increased lung permeability in +/+ and W/Wv mice, but there was no significant difference between groups. BAL PGD2 increased significantly in +/+ mice following PAF challenge (559 +/- 24 ng/ml) compared with vehicle controls (152 +/- 8 pg/ml). There was no significant increase in BAL PGD2 from W/Wv mice. Nedocromil pretreatment significantly (P < 0.05) decreased PAF-induced hyperreactivity in AKR/J mice but not in W/Wv mice (P > 0.05). We conclude that mast cells contribute significantly to PAF-induced hyperreactivity but not hyperpermeability in mice.
Longphre
M
M
Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205.
Zhang
L Y
LY
Paquette
N
N
Kleeberger
S R
SR
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001772:Blood Cell Count; D016026:Bone Marrow Transplantation / Q000502:physiology; D001980:Bronchi / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005070:Evans Blue; D006400:Hematocrit; D008168:Lung / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008806:Mice, Inbred AKR; D008817:Mice, Mutant Strains; D017835:Nedocromil / Q000494:pharmacology; D010539:Permeability; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000032:analysis; D013045:Species Specificity; D014132:Trachea / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; D017835:Nedocromil; C052518:WEB 2086; D005070:Evans Blue; D000109:Acetylcholine; D015230:Prostaglandin D2