title: IgG1-mediated acute pulmonary hypersensitivity response in the guinea pig. Involvement of specific lipid mediators.
abstract: We determined the pulmonary obstructive response to aerosolized antigen challenge, and its sensitivity to antagonists of specific lipid mediators, in IgG, passively sensitized (IgG1-PS) guinea pigs. Antiovalbumin (OA)-IgG1 was isolated by affinity chromatography from serum derived from actively immunized Hartley guinea pigs. Propranolol and pyrilamine pretreated, IgG1-PS guinea pigs were challenged with aerosolized antigen and pulmonary obstruction was quantified by measurements of excised lung gas volume (ELGV). ELGV increased between 150 and 1,035% in a dose-proportional fashion with increasing antigen exposure (0.001 to 0.1% nebulizer concentration). The leukotriene antagonists ICI-204,219 and SKF-104,353 exhibited dose-proportional inhibitions in antigen-induced elevations in ELGV, inhibiting up to 65 and 87% at the maximal concentrations examined. Similarly, the platelet-activating factor (PAF) antagonists WEB-2086 and L-659,989 inhibited antigen-induced elevations in ELGV, inhibiting up to 94 and 59% at the maximal concentrations examined. In contrast, the cyclooxygenase (CO) inhibitor piroxicam significantly enhanced (p less than 0.05) the OA-induced elevations in ELGV. Aerosolized PAF challenge produced dose-proportional elevations in ELGV that were significantly inhibited by the LTD, antagonist ICI-204,219 (38 and 43% inhibition) and the CO inhibitor piroxicam (62 and 48% inhibition) in sensitized and nonsensitized animals, respectively. We hypothesize that IgG1-dependent airway obstruction is mediated in part by LTD, produced in response to PAF generation.
authors.affiliation: Department of Immunology and Infectious Diseases, Pfizer Inc., Groton, Connecticut 06340.
authors.forename: J W
authors.initials: JW
authors.lastname: Watson
authors.forename: M
authors.initials: M
authors.lastname: Conklyn
authors.forename: H J
authors.initials: HJ
authors.lastname: Showell
mesh_terms: D000208:Acute Disease; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000494:pharmacology; D006168:Guinea Pigs; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology*; D007211:Indoles; D008055:Lipids / Q000502:physiology*; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D048448:Phenylcarbamates; D010894:Piroxicam / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000503:physiopathology*; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D001381:Azepines; D003998:Dicarboxylic Acids; D005663:Furans; D007074:Immunoglobulin G; D007211:Indoles; D008055:Lipids; D048448:Phenylcarbamates; D010972:Platelet Activating Factor; D013189:SRS-A; D013449:Sulfonamides; D014105:Tosyl Compounds; D014230:Triazoles; C052518:WEB 2086; C054893:L 659989; D010894:Piroxicam; D010047:Ovalbumin; D011433:Propranolol; D011738:Pyrilamine; C052393:pobilukast; C062735:zafirlukast