title: Inflammatory mediators involved in antigen-induced airway microvascular leakage in guinea pigs.
abstract: Antigen challenge of ovalbumin (OA)-sensitized guinea pigs results in significant (p less than 0.05) increases in vascular permeability to Evans blue (EB) dye in the airways, esophagus, and bladder. Mean values +/- SEM in ng EB/mg wet weight tissue for unsensitized versus sensitized animals were: trachea, 23.6 +/- 6.6 versus 92.5 +/- 11.1; main bronchi, 31.1 +/- 12.2 versus 153.1 +/- 14.9; "central" intrapulmonary airways (ipa), 34.6 +/- 11.2 versus 101.3 +/- 6.2; and "peripheral" ipa, 26.2 +/- 6.8 versus 93.5 +/- 13.6. We investigated the involvement of several mediators of inflammation in this process. FPL 55712, a sulfidopeptide leukotriene receptor antagonist, caused significant inhibition of leakage in trachea (to 55.1 +/- 9.8) and main bronchi (91.7 +/- 15.8). Blockade of the cyclooxygenase and lipoxygenase pathways with BW 755C, but not of the cyclooxygenase pathway alone with indomethacin, also significantly reduced EB dye extravasation in trachea (55.1 +/- 18.0), main bronchi (71.7 +/- 23.0), and "central" ipa (62.7 +/- 16.4). The histamine antagonists, chlorpheniramine and cimetidine, only inhibited microvascular leakage in main bronchi (94.4 +/- 20.0). PAF-receptor blockade with the ginkgolide mixture BN 52063 had no effect. Nedocromil sodium, a mast cell stabilizer and an inhibitor of inflammatory cell activation, caused significant inhibition throughout the airways: trachea, 50.4 +/- 10.6; main bronchi, 72.0 +/- 15.3; "central" ipa 61.0 +/- 8.6; "peripheral" ipa 41.9 +/- 12.2. Thus, histamine and lipoxygenase products (in particular, leukotrienes), but not PAF, may mediate the antigen-induced increase in vascular permeability to different degrees in differing regions of the respiratory tract in guinea pigs.
authors.affiliation: Department of Clinical Pharmacology, Brompton Hospital, London, United Kingdom.
authors.forename: T W
authors.initials: TW
authors.lastname: Evans
authors.forename: D F
authors.initials: DF
authors.lastname: Rogers
authors.forename: B
authors.initials: B
authors.lastname: Aursudkij
authors.forename: K F
authors.initials: KF
authors.lastname: Chung
authors.forename: P J
authors.initials: PJ
authors.lastname: Barnes
mesh_terms: D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001980:Bronchi / Q000098:blood supply; D002199:Capillary Permeability / Q000187:drug effects; D002744:Chlorpheniramine / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D006168:Guinea Pigs; D007114:Immunization; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology; D007783:Lactones; D007830:Larynx / Q000098:blood supply; D008297:Male; D009297:Nasal Mucosa / Q000098:blood supply; D017835:Nedocromil; D010047:Ovalbumin / Q000276:immunology; D010936:Plant Extracts / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D012137:Respiratory System / Q000098:blood supply*; D014132:Trachea / Q000098:blood supply; D001743:Urinary Bladder / Q000098:blood supply
chemical_list: D000941:Antigens; D002867:Chromones; D007783:Lactones; D010936:Plant Extracts; D011720:Pyrazoles; D015363:Quinolones; D017835:Nedocromil; C050422:BN 52063; D002744:Chlorpheniramine; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D002927:Cimetidine; C006312:FPL 55712; D010047:Ovalbumin; D007213:Indomethacin