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Eosinophil major basic protein increases membrane permeability in mammalian urinary bladder epithelium
T J Kleine1, G J Gleich, S A Lewis
1Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston, Texas 77555, USA.
The American Journal of Physiology
|August 5, 1998
Summary
Major basic protein (MBP) increases cell membrane ion permeability, disrupting epithelial barrier function. This eosinophil protein
Area of Science:
- Cell Biology
- Physiology
- Toxicology
Background:
- Eosinophil granule protein major basic protein (MBP) exhibits toxicity via poorly understood mechanisms.
- Investigating MBP's role in altering cell membrane permeability is crucial for understanding its cytotoxic effects.
Purpose of the Study:
- To determine if major basic protein (MBP) action involves changes in membrane permeability.
- To elucidate the mechanism of MBP-induced toxicity on epithelial cell membranes.
Main Methods:
- Utilized transepithelial voltage-clamp techniques on rabbit urinary bladder epithelium.
- Applied purified MBP to the mucosal solution and monitored changes in apical membrane conductance.
- Investigated the effects of varying voltage gradients, ion concentrations (Ca2+, Mg2+), and exposure duration.
Main Results:
- Nanomolar MBP concentrations increased apical membrane conductance when the voltage was cell interior negative.
- MBP-induced conductance was nonselective for K+ and Cl-, concentration-dependent, and voltage-sensitive.
- Mucosal Ca2+ reversed, while Mg2+ partially blocked the induced conductance; prolonged exposure led to irreversible barrier loss.
Conclusions:
- Increased cell membrane ion permeability is an initial step in major basic protein (MBP)-induced loss of epithelial barrier function.
- MBP's mechanism of toxicity involves direct alteration of ion channel activity in cell membranes.