IgG1-mediated acute pulmonary hypersensitivity response in the guinea pig. Involvement of specific lipid mediators.
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.
Watson
J W
JW
Department of Immunology and Infectious Diseases, Pfizer Inc., Groton, Connecticut 06340.
Conklyn
M
M
Showell
H J
HJ
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
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