THE EFFECT OF NITROGEN-DIOXIDE ON TRACHEAL UPTAKE AND TRANSPORT OF HORSERADISH-PEROXIDASE IN THE GUINEA-PIG

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Abstract
The effect of 5 and 15 ppm of NO2 [an environmental contaminant] on airway transepithelial permeability to horseradish peroxidase (HRP) (MW, .apprx. 40,000 daltons) was studied in the guinea pig. Age- and sex-matched guinea pigs (34) were exposed to NO2 for 2 and for 14 days. In the control guinea pigs, 0.05% of the intratracheally instilled dosage of HRP was present in the plasma within 10 min, as detected by radioimmunoassay, and increased thereafter at a mean rate of 0.0016%/min. After exposure to NO2, there was a significant increase in the rate of plasma HRP accumulation (P < 0.05) with the maximal increase detected in the group exposed to 15 ppm of NO2 for 2 days. The morphologic correlates of increased permeability to HRP appear to be an increase in pinocytotic activity within the hyperplastic goblet cells, and transjunctional transport by leaky tight junctions that was noted only in animals exposed to 15 ppm for 14 days (P < 0.01). Pinocytotic vesicular transport of proteins in the secretory cells of the airways may be an important mechanism for the movement of exogenous nonlipid soluble macromolecules across the epithelial barrier.