Study of airway epithelial permeability with dextran

We studied the penetration of fluorescein isothiocyanate (FITC) T-40 dextran into the paracellular spaces in the tracheal mucosa and its appearance in the blood plasma of guinea pigs exposed to cigarette smoke or (controls) breathing room air. Under general anesthesia, the dextran solution was instilled onto the tracheal surface via a tracheotomy tube, arterial blood was sampled serially for 40 min, and then the trachea was fixed by perfusion or immersion. Examination of the tracheal mucosa with light microscopy, with and without epifluorescence, and transmission electron microscopy, revealed dextran in the paracellular spaces in mucosa from experimental animals but not controls. In all control animals, the levels of the dextran in plasma was below the sensitivity of the assay. By contrast, dextran levels in the plasma from the experimental animals fell within the sensitivity range of the assay and increased in blood at a rate of 0.00125 +/- 0.00023 (SE) expressed as a percentage of the instilled dose/min. We conclude that FITC T-40 dextran provides a reliable, fairly simple, fast method for assessing major, but not subtle, changes in paracellular permeability of the tracheal mucosa.