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Rat mesangial cells have a selective role in macrophage recruitment and activation
P J Largen1, F W Tam, A J Rees
1Department of Histopathology, St. Mary's Hospital Medical School, London, UK.
Abstract:
In proliferative glomerulonephritis glomeruli are the target of an inflammatory reaction involving macrophage recruitment and activation. We examined the role of mesangial cells in this process. Supernatants from basal, IL-1, IFN-tau or LPS-stimulated rat mesangial cells (MCS) were tested for chemotactic, colony-stimulating and activation effects on macrophages in vitro. IL-1-stimulated MCS produced a macrophage chemoattractant (p = 0.007 compared with basal MCS) and MCP-1 mRNA was detected in IL-1-stimulated mesangial cells. LPS or IL-1-stimulated MCS produced colony-stimulating activity (LPS p < 0.05, IL-1 p < 0.01, compared with basal MCS or control supernatant, CS). Macrophage activation, assessed by nitric oxide generation, was suppressed. This evidence from functional bioassays supports a selective role for mesangial cells in the control of macrophage-induced glomerular injury, whereby activated mesangial cells participate in the recruitment and proliferation of infiltrating macrophages, and suppresses at least one field of macrophage activation, namely nitric oxide generation.
Insights
Mesangial cells (MCS) influence kidney inflammation by attracting macrophages and promoting their proliferation. Activated MCS also suppress nitric oxide generation, selectively modulating macrophage activity in proliferative glomerulonephritis.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Proliferative glomerulonephritis involves inflammatory responses within the glomeruli.
- Macrophage recruitment and activation are key components of this inflammatory process.
Purpose of the Study:
- To investigate the specific role of mesangial cells (MCS) in regulating macrophage behavior during glomerular inflammation.
- To determine if MCS supernatants influence macrophage chemotaxis, proliferation, and activation.
Main Methods:
- Mesangial cells were stimulated with Interleukin-1 (IL-1), Interferon-tau (IFN-tau), or Lipopolysaccharide (LPS).
- Supernatants from stimulated MCS were tested for effects on macrophage chemotaxis, colony-stimulating activity, and nitric oxide generation in vitro.
- Monocyte Chemoattractant Protein-1 (MCP-1) mRNA expression in MCS was analyzed.
Main Results:
- IL-1-stimulated MCS produced a significant macrophage chemoattractant, with MCP-1 mRNA detected.
- LPS and IL-1 stimulation of MCS resulted in increased colony-stimulating activity.
- Macrophage activation, indicated by nitric oxide generation, was suppressed by MCS supernatants.
Conclusions:
- Activated mesangial cells play a selective role in controlling macrophage-induced glomerular injury.
- MCS contribute to macrophage recruitment and proliferation.
- MCS can suppress certain aspects of macrophage activation, such as nitric oxide production.