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Stimulation of rat mesangial cell proliferation by macrophage interleukin 1
Abstract:
Conditioned media from LPS-activated rat peritoneal macrophages enhanced the proliferation rates of cultured rat glomerular mesangial cells. This macrophage-derived activity extensively co-purified with interleukin 1 (IL 1) activity through sequential ammonium sulfate precipitation, S-200 gel chromatography, DEAE-cellulose anion exchange chromatography, and phenyl-Sepharose chromatography. In addition, the macrophage-derived factor was heat-labile (80 degrees C) and inactivated by phenylglyoxal, thus allowing tentative identification as IL 1. Macrophage supernatants and purified IL 1 enhanced the proliferative rates of mesangial cells only in the presence of serum; the use of platelet-poor plasma or serum depleted of platelet-derived growth factor was without effect. IL 1 acted to increase the percentage of cycling cells, without a change in the length of the individual cell cycle times. These findings provide a potential mechanism whereby activated macrophages, in combination with platelet factors, enhance mesangial cell proliferation. Such processes may contribute to the mesangial hypercellularity frequently found in immune-mediated glomerulonephritis.
Insights
Activated macrophages release interleukin 1 (IL 1), which, with platelet factors, promotes glomerular mesangial cell proliferation. This may explain hypercellularity in glomerulonephritis.
Area of Science:
- Immunology
- Cell Biology
- Nephrology
Background:
- Glomerular mesangial cell proliferation is a key feature of glomerulonephritis.
- Macrophages are implicated in the pathogenesis of inflammatory kidney diseases.
Purpose of the Study:
- To investigate the role of macrophage-derived factors in regulating mesangial cell proliferation.
- To identify the specific factor responsible for enhanced mesangial cell growth.
Main Methods:
- Cultured rat peritoneal macrophages were activated with LPS.
- Conditioned media were analyzed for mitogenic activity on mesangial cells.
- Macrophage-derived activity was purified using sequential chromatography.
- Characterization included heat lability and inactivation by phenylglyoxal.
Main Results:
- Macrophage-conditioned media significantly enhanced mesangial cell proliferation.
- The active factor co-purified with interleukin 1 (IL 1) and shared its properties (heat-lability, phenylglyoxal inactivation).
- IL 1-induced proliferation required the presence of serum factors, particularly platelet-derived growth factor.
Conclusions:
- Activated macrophages produce IL 1, which stimulates mesangial cell proliferation in conjunction with platelet-derived growth factors.
- This interaction provides a potential mechanism for mesangial hypercellularity in immune-mediated glomerulonephritis.