Passive sensitization of human airways induces myogenic contractile responses in vitro.
We assessed effects of passive sensitization on human bronchial smooth muscle (BSM) response to mechanical stretching in vitro. Bronchial rings were sham (control) or passively sensitized overnight by using sera from donors demonstrating sensitivity to Dermatophagoides farinae and having immunoglobulin E (IgE) concentrations of 2,600 +/- 200 U/ml. Tissues were fixed isometrically to force transducers to measure responses to electrical field stimulation (EFS) and quick stretch (QS). The myogenic response to QS was normalized to the maximal response to EFS (%EFS). The myogenic response of sensitized BSM was 47.9 +/- 10.9 %EFS to a QS of approximately 6.5% optimal length (Lo); sham-sensitized tissues had a myogenic response of 13.5 +/- 6.4 %EFS (P = 0.012 vs. passively sensitized). A QS of approximately 13% Lo in sensitized BSM caused a response of 82.8 +/- 20.9 %EFS; sham-sensitized tissues developed a response of 38.2 +/- 17.3 %EFS (P = 0.004). BSM incubated with serum from nonallergic donors did not demonstrate increased QS response (4.6 +/- 1.4 %EFS, P = not significant vs. tissue exposed to atopic sera). However, tissues incubated in sera from nonatopic donors supplemented with hapten-specific chimeric IgE (JW8) demonstrated augmented myogenic response to QS of approximately 6.5% Lo (21.9 +/- 6.2 %EFS, P = 0. 027 vs. nonatopic sera alone). We demonstrate that passive sensitization of human BSM preparations causes induction and augmentation of myogenic contractions to QS; this hyperresponsiveness corresponds to the IgE concentration in sensitizing sera.
Mitchell
R W
RW
Asthma, Allergy, and Immunological Disease Research Center, The University of Chicago, Chicago, Illinois 60637, USA.
Rabe
K F
KF
Magnussen
H
H
Leff
A R
AR
D000485:Allergens / Q000633:toxicity; D001980:Bronchi / Q000276:immunology / Q000503:physiopathology*; D004558:Electric Stimulation; D006801:Humans; D007116:Immunization, Passive; D007073:Immunoglobulin E / Q000276:immunology / Q000502:physiology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000503:physiopathology*; D011661:Pulmonary Stretch Receptors / Q000502:physiology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000503:physiopathology*
D000485:Allergens; D007073:Immunoglobulin E