The effect of nitrogen dioxide on tracheal uptake and transport of horseradish peroxidase in the guinea pig.

The effect of 5 and 15 ppm of nitrogen dioxide (NO2) on airway transepithelial permeability to horseradish peroxidase (HRP) (molecular weight, approximately 40,000 daltons) was studied in the guinea pig. Age- and sex-matched guinea pigs (n = 34) were exposed to NO2 for 2 and for 14 days. In the control guinea pigs, 0.05% of the intratracheally instilled dosage HRP was present in the plasma within 10 min, as detected by radioimmunoassay, and increased thereafter at amean 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 (a) an increase in pinocytotic activity within the hyperplastic globlet cells, and (b) transjunctional transport by leaky tight junctions that was noted only in animals exposed to 15 ppm for 14 days (p < 0.01). Our data suggests that pinocytotic vesicular transport of proteins in the secretory cells of the airway may be an important mechanism for the movement of exogenous nonlipid soluble macromolecules across the epithelial barrier.