Studying human airway pharmacology in microsections: application of videomicrometry.
The influence of endogenously-released mediators and activated eosinophils on the airway lumen and the effect of passive sensitization on anti-immunoglobulin (Ig)-E-induced contractile responses was investigated by videomicrometry. Human bronchial sections of 2-3 mm internal diameter, placed in 250 microL Hank's balanced salt solution on microtitre plates, were monitored and recorded by digitized image analysis. Airway preparations exhibited a spontaneous narrowing (mean+/-SEM -33+/-5% of the luminal area). Removal of the bronchial epithelium almost completely prevented the development of spontaneuous narrowing (-6+/-3%; p<0.001). The addition of platelet-activating factor stimulated human eosinophils to the bronchial sections led to significant narrowing of the airway lumen (-39+/-9%; p<0.05). Passive sensitization induced hyperresponsiveness to polyclonal anti-IgE (-35+/-8%; p<0.01). It is concluded that videomicrometry is suitable for studying interactions between human airways and inflammatory cells, as well as the effect of passive sensitization on smooth muscle reactivity in vitro, without the imposition of preload. Under these conditions, human airways exhibited a spontaneous decrease of the airway lumen over time suggesting a role for epithelium-derived mediators because the development of spontaneous tone was epithelium dependent.
Schmidt
D T
DT
Leiden University Medical Centre, Dept of Pulmonology, The Netherlands.
Dent
G
G
Rühlmann
E
E
Muñoz
N M
NM
Leff
A R
AR
Rabe
K F
KF
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects / Q000276:immunology; D004804:Eosinophils / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D018715:Microscopy, Video / Q000379:methods*; D008867:Microtomy; D020545:Respiratory Mucosa / Q000187:drug effects / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; C026408:anti-IgE antibodies; D006632:Histamine