Related Experiment Videos
Vascular endothelial cell killing by combinations of membrane-active agents and hydrogen peroxide
I Ginsburg1, D F Gibbs, L Schuger
1Department of Oral Biology, Hadassah School of Dental Medicine, Hebrew University, Jerusalem, Israel.
Abstract:
Previous studies have demonstrated that a number of membrane-active agents are capable of binding to the surface of polymorphonuclear leukocytes (PMN) resulting in an augmentation of superoxide anion and hydrogen peroxide (H2O2) production in response to soluble stimuli. It is now demonstrated that these same membrane-active agents can bind to the surface of endothelial cells and enhance their susceptibility to killing by H2O2. Membrane-active agents which are capable of synergizing with H2O2 include cationic proteins, cationic poly-amino acids, lysophosphatides and enzymes which are capable of degrading membrane phospholipids (e.g., phospholipase C, phospholipase A2 and streptolysin S). In each case, treatment of the target cells with the membrane-active agent and H2O2 produces greater damage than the sum of the damage produced by either agent separately. Since inflammatory lesions, particularly sites of bacterial infection, may contain a rich mixture of cationic substances, phospholipases and phospholipid breakdown products, these substances may contribute to the tissue damage observed at sites of inflammation by enhancing endothelial cell sensitivity to PMN-generated H2O2 as well as by augmenting the generation of H2O2 by PMNs.
Insights
Certain membrane-active agents increase endothelial cell sensitivity to hydrogen peroxide (H2O2) and augment damage. These findings suggest a role in inflammation and tissue injury.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Membrane-active agents augment superoxide anion and hydrogen peroxide (H2O2) production by polymorphonuclear leukocytes (PMN).
- These agents bind to PMN surfaces, enhancing their response to stimuli.
Purpose of the Study:
- To investigate the effect of membrane-active agents on endothelial cells.
- To determine if these agents enhance endothelial cell susceptibility to H2O2-mediated killing.
Main Methods:
- Treatment of endothelial cells with various membrane-active agents (cationic proteins, poly-amino acids, lysophosphatides, phospholipase C, phospholipase A2, streptolysin S).
- Co-treatment with hydrogen peroxide (H2O2).
- Assessment of cell damage and H2O2-mediated killing.
Main Results:
- Membrane-active agents bind to endothelial cells, increasing their susceptibility to H2O2.
- Synergistic damage observed when cells are treated with both membrane-active agents and H2O2.
- Agents include cationic proteins, poly-amino acids, lysophosphatides, and phospholipid-degrading enzymes.
Conclusions:
- Membrane-active agents enhance endothelial cell sensitivity to H2O2, leading to increased cell damage.
- These agents may contribute to tissue injury at inflammatory sites by sensitizing endothelial cells to PMN-derived H2O2.
- The presence of cationic substances, phospholipases, and phospholipid breakdown products in inflammatory lesions could exacerbate tissue damage.