title: Passive sensitization of human airways increases responsiveness to leukotriene C4.
abstract: Passive sensitization of human airways in vitro causes increased responsiveness to histamine and induces specific immunoglobulin (Ig)E-dependent contractile responsiveness to allergen. Leukotrienes (LTs) and, to a lesser extent, histamine are the major mediators of allergen-induced contraction. Since it is unclear whether passively sensitized airways are also hyperresponsive to cysteinyl leukotrienes, this study investigated the effect of passive sensitization on LTC4-, in addition to histamine- and allergen-induced contractions in vitro. Bronchial rings from nine nonatopic patients were sensitized overnight with serum containing high levels of total IgE (>250 U x mL(-1)) and allergen-specific IgE against Dermatophagoides farinae (fluorescence allergosorbent test) (FAST class > or =3). The potency (-log10 of the mediator concentration causing a half maximal response (pEC50) of histamine was significantly increased in serum-sensitized tissues compared to nonsensitized controls ((mean+/-SEM) pEC50 5.20+/-0.27 versus 5.64+/-0.18; p=0.02) and maximal contractions were enhanced (877+/-47 versus 543+/-51 mg; p<0.0001). Similarly, the potency of LTC4 was significantly increased in sensitized compared to nonsensitized bronchial rings (pEC50 9.37+/-0.20 versus 8.66+/-0.26; p=0.004); maximal contractions were also enhanced (811+/-57 versus 361+/-86 mg; p<0.0001). These data demonstrate that passive sensitization of human airways induces an increase not only in histamine but also in leukotriene responsiveness. Therefore, it might be speculated that allergen responses in sensitized airways are effected through a combination of increased mediator release from inflammatory cells and increased responsiveness of airway smooth muscle.
authors.affiliation: Leiden University Medical Center, Dept of Pulmonology, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Schmidt
authors.forename: E
authors.initials: E
authors.lastname: Ruehlmann
authors.forename: D
authors.initials: D
authors.lastname: Branscheid
authors.forename: H
authors.initials: H
authors.lastname: Magnussen
authors.forename: K F
authors.initials: KF
authors.lastname: Rabe
mesh_terms: D000328:Adult; D000368:Aged; D000485:Allergens / Q000276:immunology*; D001249:Asthma / Q000276:immunology; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D017997:Leukotriene C4 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012130:Respiratory Hypersensitivity / Q000276:immunology
chemical_list: D000485:Allergens; D017997:Leukotriene C4; D007073:Immunoglobulin E; D006632:Histamine; D002217:Carbachol; D007545:Isoproterenol