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Glomerular mesangium. Analysis of the increased activity observed in experimental acute aminonucleoside nephrosis in
Abstract:
Kinetic studies have revealed increased mesangial macromolecular uptake in acute aminonucleoside of puromycin (PAN) nephrosis in the rat. The mechanisms leading to this increased activity, however, are poorly understood. Therefore, we studied mesangial function and ultrastructure in rats 8 days after intravenous injection of 6 mg. of PAN per 100 gm. of body weight. One hour after intravenous injection of 20 mg. of colloidal carbon per 100 gm., no differences in mesangial carbon could be detected between PAN rats and controls. After 24 hours, the amount of mesangial carbon was significantly higher in PAN rats; rates of disappearance did not differ. Ultrastructural examination revealed no differences in localization of mesangial carbon at the 1-hour interval. After 24 hours, mesangial cells of PAN rats showed an increased number of lysosomes filled with carbon; the number of carbon particles in the mesangial matrix was not increased. Using an ultrastructural immunoperoxidase technique, we found increased amounts of endogenous IgG in the extracellular space of segmental mesangial lobules of PAN rats. IgG was mainly present in matrix substance of electron-lucent aspect, and quantitative morphometric analysis revealed an increase in volume of this loose permeable matrix component (mesangial channels). No increased staining of IgG was found in the lacis area indicating that there was no increased mesangial egress of macromolecules in PAN nephrosis. The increased volume of the permeable mesangial channels in segmental mesangial lobules of PAN rats may lead to a pooling of tracer material with consequent increased phagocytosis by mesangial cells.
Insights
Aminonucleoside of puromycin (PAN) nephrosis increases mesangial macromolecular uptake in rats. This is due to expanded permeable mesangial channels, leading to greater mesangial cell phagocytosis.
Area of Science:
- Nephrology
- Pathology
- Cell Biology
Background:
- Aminonucleoside of puromycin (PAN) nephrosis is characterized by increased mesangial macromolecular uptake.
- The underlying mechanisms driving this uptake remain unclear.
Purpose of the Study:
- To investigate mesangial function and ultrastructure in rats with PAN nephrosis.
- To elucidate the mechanisms behind increased mesangial macromolecular uptake.
Main Methods:
- Rats were injected with aminonucleoside of puromycin (PAN) to induce nephrosis.
- Colloidal carbon was used as a tracer to assess macromolecular uptake and localization.
- Ultrastructural examination and immunoperoxidase techniques were employed.
Main Results:
- PAN rats showed significantly higher mesangial carbon accumulation at 24 hours compared to controls.
- Ultrastructural analysis revealed increased lysosomes with carbon in mesangial cells of PAN rats.
- Increased endogenous IgG and expanded permeable mesangial channels were observed in PAN nephrosis.
Conclusions:
- The increased volume of permeable mesangial channels in PAN nephrosis contributes to macromolecular pooling.
- This pooling enhances phagocytosis by mesangial cells, explaining increased uptake.
- No evidence of increased mesangial egress of macromolecules was found.