HOCl effects on tracheal epithelium: Conductance and permeability measurements

It is speculated that hypochlorous acid (HOCl), produced by neutrophils, can disrupt the tracheal epithelial barrier without damage to epithelial cells. This was investigated with solute permeability (P) and electrical conductance (G) measurements on tracheae from 4-wk-old rabbits. A new system for epithelial bioelectric measurements on intact tracheae was developed and validated. Control values of G, short-circuit current, and spontaneous potential difference were 4.9 ± 0.5 (SE) mS/cm², 42.6 ± 4.7 μA/cm², and 8.9 ± 1.0 mV (lumen negative), respectively (n = 5). Control P values for sucrose, inulin, and Dextran-20 were 5.14 ± 0.48, 0.63 ± 0.10, and 0.057 ± 0.007 x 10^-7 cm/s, respectively (n = 6). Tracheae treated with HOCl showed the same dose response for G and P: 0.6 mM HOCl had no effect; 6 mM HOCl, a concentration that could exist in infected airways, significantly increased both P and G (about two- to fourfold) without damage to epithelial cells; and 12 and 30 mM HOCl caused more than 10-fold increases for both P and G with cell disruption. Vitamin C blocked epithelial damage caused by 30 mM HOCl. Tracheae from 1-wk-old rabbits were significantly more sensitive to HOCl than those from 4-wk-old or adult rabbits. This study validated a new bioelectric measurement system and showed that HOCl has both dose- and age-dependent effects on the tracheal epithelium.