title: Antigen-dependent leukotriene synthesis and histamine release from IgG1 passively-sensitized guinea pig lungs ex vivo: relationship between serum levels of antigen-specific IgG1 and mediator synthesis/release.
abstract: Naive guinea-pigs were passively sensitized with varying amounts of affinity column purified, homologous, anti-ovalbumin IgG1 (anti-OA IgG1) and then examined for a) the capacity of lung tissue to release mediators (histamine and LTB4/LTD4) in response to antigen-challenge ex vivo and b) the attendant circulating levels of anti-OA IgG1. Intraperitoneal administration of anti-OA IgG1 (0.125-0.75 mg/kg) to guinea-pigs facilitated the synthesis of LTB4 (8-25 ng/g lung) and LTD4 (18-80 ng/g) and the release of histamine (1-7 ug/g) from lung tissue after exposure to 10 micrograms/ml of ovalbumin for 20 min ex vivo. Peak levels of mediators were found using 0.5 mg/kg anti-OA IgG1 with an ED50 = 0.35 mg/kg. LTD4/LTB4 synthesis and histamine release were both antigen concentration- and time-dependent, and LT synthesis was observable in non-perfused lungs and in lungs perfused free of blood. Maximum sensitization occurred at 1-2 days post i.p. administration of anti-OA IgG1 and was maintained up to 7 days. Measurement of anti-OA IgG1 using an enzyme-linked immunosorbent assay demonstrated that circulating antibody levels were 2-6 micrograms/ml at the doses which caused sensitization. The level of anti-OA IgG1 found in passively sensitized animals was at least 100-fold less than that found in actively-sensitized guinea-pigs despite the similar magnitude in LTD4/LTB4 synthesized and the amount of histamine released. Using purified antibody, the results demonstrate that in guinea-pigs, IgG1 can play a prominent role in regulating lung LT synthesis and histamine release, and that microgram per ml circulating levels of this antibody are sufficient to sensitize naive lungs.
authors.affiliation: Department of Immunology and Infectious Diseases, Pfizer Inc., Groton, Connecticut 06340.
authors.forename: J B
authors.initials: JB
authors.lastname: Cheng
authors.forename: J S
authors.initials: JS
authors.lastname: Pillar
authors.forename: M J
authors.initials: MJ
authors.lastname: Conklyn
authors.forename: R
authors.initials: R
authors.lastname: Breslow
authors.forename: J T
authors.initials: JT
authors.lastname: Shirley
authors.forename: N P
authors.initials: NP
authors.lastname: Gerard
authors.forename: H J
authors.initials: HJ
authors.lastname: Showell
mesh_terms: D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D006168:Guinea Pigs; D006636:Histamine Release / Q000276:immunology*; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000096:biosynthesis*; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D008297:Male; D010047:Ovalbumin / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D015289:Leukotrienes; D010047:Ovalbumin; D001094:Arachidonate 5-Lipoxygenase