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Histones evoke thymocyte death in vitro; histone-binding immunoglobulins decrease their cytotoxicity
D N Abakushin1, I A Zamulaeva, A M Poverenny
1Department of Radiation Biochemistry, Medical Radiological Research Center, Russian Academy of Medical Sciences, Obninsk, Kaluga Region, 249020, Russia. dna@obninsk.su
Biochemistry. Biokhimiia
|July 9, 1999
Summary
Positively charged molecules like histones and poly-L-lysine are toxic to rat thymocytes, disrupting cell membranes. Human immunoglobulins can bind histones, reducing thymocyte death and suggesting cytotoxicity is epitope-dependent.
Area of Science:
- Cell Biology
- Immunology
- Biochemistry
Background:
- Cell membrane integrity is crucial for thymocyte function.
- Polycationic molecules can interact with cell membranes.
- Understanding these interactions is vital for immunology and drug development.
Purpose of the Study:
- To investigate the cytotoxic effects of various polycationic molecules on rat thymocytes.
- To determine the protective role of human immunoglobulins against histone-induced cytotoxicity.
- To elucidate the mechanism underlying the cytotoxicity of charged biomolecules.
Main Methods:
- Incubation of intact rat thymocytes with histones, poly-L-lysine, spermine, and thymohexine.
- Assessment of cell membrane permeability and cell death.
- Analysis of immunoglobulin binding to histones and thymocytes.
- Dose- and time-dependent effect studies.
Main Results:
- Histones and poly-L-lysine induced significant thymocyte cytotoxicity, altering membrane permeability.
- Human immunoglobulins bound to histones but not to intact thymocytes.
- Immunoglobulins reduced histone-induced thymocyte death.
- Increased cell-associated immunoglobulin was observed in the presence of histone.
Conclusions:
- Cytotoxicity of polycationic molecules like histones is mediated by membrane damage.
- Human immunoglobulins can mitigate histone-induced thymocyte death.
- The extent of cytotoxicity correlates with the availability of cell surface epitopes for charged molecule interaction.