ACELL Mar. 45/3

Kleine, Teri J., Gerald J. Gleich, and Simon A. Lewis. Eosinophil peroxidase increases membrane permeability in mammalian urinary bladder epithelium. Am. J. Physiol. 276 (Cell Physiol. 45): C638–C647, 1999.—Eosinophil peroxidase (EPO), a cationic protein found in eosinophils, has been reported to be cytotoxic independent of its peroxidase activity. This study investigated with electrophysiological methods whether EPO is toxic to mammalian urinary bladder epithelium. Results indicate that EPO, when added to the mucosal solution, increases apical membrane conductance of urinary bladder epithelium only when the apical membrane potential is cell interior negative. The EPO-induced conductance was concentration dependent, with a maximum conductance of 411 μS/cm2 and a Michaelis-Menten constant of 113 nM. The EPO-induced conductance was nonselective for K1 and Cl2. The conductance was partially reversed using voltage but not by removal of EPO from the bulk solution. Mucosal Ca21 reversed the EPO-induced conductance by a mechanism involving reversible block of the conductance. Prolonged exposure (up to 1 h) to EPO was toxic to the urinary bladder epithelium, as indicated by an irreversible increase in transepithelial conductance. These results suggest that EPO is indeed toxic to urinary bladder epithelium via a mechanism that involves an increase in membrane permeability.