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Ex Vivo Red Blood Cell Hemolysis Assay for the Evaluation of pH-responsive Endosomolytic Agents for Cytosolic Delivery of Biomacromolecular Drugs
Published on: March 9, 2013
THE MECHANISM OF THE INHIBITION OF HEMOLYSIS.
1The Nassau Hospital, Mineola, Long Island.
The Journal of General Physiology
|October 30, 2009
Summary
Plasma and serum inhibit red blood cell hemolysis similarly to sugars and electrolytes. These effects, along with accelerations, stem from interactions with the red cell membrane, influencing its breakdown by lysins.
Area of Science:
- Biochemistry
- Cell Biology
- Hematology
Background:
- Hemolysis, the breakdown of red blood cells, can be influenced by various substances.
- Plasma and serum are known to affect hemolytic processes.
- Previous studies have investigated acceleratory effects on hemolysis.
Purpose of the Study:
- To investigate the inhibitory effects of plasma and serum on hemolysis.
- To compare these inhibitory effects with those of sugars, electrolytes, and known accelerators.
- To elucidate the mechanism of inhibition and acceleration at the red cell membrane level.
Main Methods:
- Studying hemolysis induced by saponin and other lysins.
- Analyzing the effects of plasma, serum, sugars, electrolytes, indol, and benzene.
- Measuring the inhibitory constant (R) and its relationship to inhibitor concentration.
- Investigating the temperature coefficient and dependence on red cell type.
Main Results:
- Plasma/serum inhibition of hemolysis is mechanistically similar to inhibition by sugars/electrolytes and acceleration by indol/benzene.
- Inhibitory and acceleratory effects result from reactions between modifiers and red cell membrane components targeted by lysins.
- The inhibitory constant (R) is linearly dependent on inhibitor concentration and influenced by lysin concentration and red cell type.
- Inhibition is not solely dependent on the protein content of plasma/serum.
Conclusions:
- Hemolysis, acceleration, and inhibition involve interactions between lysins, accelerators, inhibitors, and red cell membrane components.
- The red cell membrane is an ultrastructure with varying resistance, initiating lysis at the least resistant points.
- Accelerators/inhibitors likely alter lysin concentration at the membrane surface or partitioning, involving reversible and irreversible binding to membrane components.
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