Vol. 276, Issue 3, C638-C647, March 1999
Eosinophil peroxidase increases membrane permeability in
mammalian urinary bladder epithelium
Teri J.
Kleine1,
Gerald J.
Gleich2, and
Simon A.
Lewis1
1 Department of Physiology and
Biophysics, University of Texas Medical Branch, Galveston, Texas
77555; and 2 Department of
Immunology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
55905
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 K+ and
Cl
. The conductance was
partially reversed using voltage but not by removal of EPO from the
bulk solution. Mucosal Ca2+
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.
cationic proteins; tight epithelium; cytotoxic protein; ion
conductance; calcium
