Am. J. Respir. Crit. Care Med., Vol 153, No. 2, Feb 1996, 841-846.
Permeability of human isolated airways increases after hydrogen peroxide and poly-L-arginine
AR Hulsmann, HR Raatgeep, JC den Hollander, WH Bakker, PR Saxena and JC de Jongste
Department of Pediatrics, Erasmus University, Rotterdam, The Netherlands.
In asthma, the airway epithelium may be damaged by oxidants and cationic
proteins produced by eosinophils. The degree of epithelial damage
correlates with the level of bronchial hyperreactivity. An increase in
airway permeability to bronchoactive agonists may be one of the factors
responsible for airway hyperresponsiveness in asthma. We investigated the
effects of the oxidant hydrogen peroxide and the major basic protein (MPB)
analogue poly-L-arginine on the permeability and morphology of nonasthmatic
human peripheral airways. In addition, we examined whether airway
permeability depends on airway size. Human airway tubes (generation 7 to
12) mounted in an organ bath were luminally perfused with Krebs-Henseleit
buffer containing the hydrophilic tracer 111In-diethyletriamine pentaacetic
acid (111In-DTPA) or the lipophilic tracer 14C-antipyrine (14C-AP).
Permeability of the airways was calculated from the fluxes of the tracer
molecules across the airway wall. After experiments, light- and
electromicroscopic examination of the airway epithelium was performed.
Baseline permeability to 14C-AP was five times greater than to 111In-DTPA.
Luminal exposure of the airways to 100 mmol/L H2O2 produced a significant,
sixfold increase in permeability to 111In-DTPA but not to 14C-AP,
indicating the opening of paracellular pathways. The H2O2- induced increase
in permeability was partly reversible. Luminal exposure to polyarginine for
3 h and 16 h produced a significant 4.5- and 7-fold increase in
permeability to 111In-DTPA, respectively. Histologic examination of
epithelium exposed to H2O2 of poly-L-arginine showed focal loss of
superficial cells with preservation of basal cells. Baseline airway
permeability increased with decreasing airway size (rs = -0.75, p <
0.01). These results suggest that epithelial damage due to eosinophil
products may increase airway permeability, and that this may at least
partly explain the increased responsiveness to inhaled stimuli in asthma.
