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Rat mesangial cell lysis in vitro is induced by cationic polypeptides
1Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
The American Journal of Pathology
|February 1, 1993
Summary
Cationic bovine gamma-globulin (BGG) causes kidney cell injury and releases enzymes that degrade basement membranes. Heparin sodium prevents this damage, suggesting charge alone isn't sufficient for cytotoxicity.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Immune complex glomerulonephritis can be induced by cationic proteins.
- Cationic bovine gamma-globulin (BGG) is implicated in this process.
- Understanding the cellular mechanisms of BGG-induced injury is crucial.
Purpose of the Study:
- To investigate the in vitro effects of cationic BGG on rat mesangial cells.
- To determine the role of charge and molecular weight in polycation-induced cytotoxicity.
- To explore potential inhibitory mechanisms against BGG-induced cell damage.
Main Methods:
- Exposure of rat mesangial cells to cationic (c) and native (n) BGG.
- Measurement of lysosomal beta-glucuronidase and lactate dehydrogenase (LDH) release.
- Assessment of morphological changes and the effects of heparin sodium and polycations of varying molecular weights.
Main Results:
- Cationic BGG induced significant release of beta-glucuronidase and LDH, indicating cell injury.
- Native BGG did not cause significant cell damage.
- Polycations with higher molecular weight (>50 kd) induced LDH release, while lower molecular weights did not.
- Anionic heparin sodium inhibited cBGG-induced injury, but only when added concurrently.
Conclusions:
- Cationic charge is necessary but not sufficient for polycations to induce cytotoxicity.
- The rapid cell swelling and LDH release suggest direct plasma membrane destruction by cBGG.
- Altered sodium ion concentrations may play a role in the observed cytotoxicity.