Eosinophil major basic protein increases membrane permeability in mammalian urinary bladder epithelium.
The eosinophil granule protein major basic protein (MBP) is toxic to a wide variety of cell types, by a poorly understood mechanism. To determine whether the action of MBP involves an alteration in membrane permeability, we tested purified MBP on rabbit urinary bladder epithelium using transepithelial voltage-clamp techniques. Addition of nanomolar concentrations of MBP to the mucosal solution caused an increase in apical membrane conductance only when the voltage across the apical membrane was cell interior negative. The magnitude of the MBP-induced conductance was a function of MBP concentration, and the rate of the initial increase in conductance was a function of the transepithelial voltage. The MBP-induced conductance was nonselective for K+ and Cl-. Mucosal Ca2+ reversed the induced conductance, whereas mucosal Mg2+ partially blocked the induced conductance and slowed the rate of the increase in conductance. The induced conductance was partially reversed by changing the voltage gradient across the apical membrane to cell interior positive. Prolonged exposure resulted in an irreversible loss of the barrier function of the urinary bladder epithelium. These results suggest that an increase in cell membrane ion permeability is an initial step in MBP-induced loss of barrier function.
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston, Texas 77555, USA.
T J
TJ
Kleine
G J
GJ
Gleich
S A
SA
Lewis
D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D004553:Electric Conductivity; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009092:Mucous Membrane / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011817:Rabbits; D012260:Ribonucleases; D013997:Time Factors; D001743:Urinary Bladder / Q000502:physiology*
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D018836:Inflammation Mediators; D012260:Ribonucleases