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Glomerular expression of monocyte chemoattractant protein-1 in experimental and human glomerulonephritis
1Department of Medicine, Ohio State University School of Medicine, Columbus.
Background:
Glomerular monocytes are found in a variety of renal diseases and appear to be important in the pathogenesis of glomerular injury. The mediators responsible for recruiting monocytes to the glomerulus are not well characterized. We have recently established that cultured human mesangial cells produce the specific monocyte chemoattractant, monocyte chemoattractant protein-1 (MCP-1) in response to inflammatory cytokines commonly found in glomeruli during glomerulonephritis (GN). This suggested that MCP-1 may be involved in recruiting leukocytes to the glomerulus. To date however, there is little information regarding the expression of MCP-1 during renal disease. The present study was undertaken to investigate the in vivo expression of MCP-1 during experimental and human GN.
Experimental Design:
A rodent model of anti-glomerular basement membrane GN was used to investigate glomerular MCP-1 mRNA regulation and protein expression. The presence of MCP-1 in human renal tissue was studied by immunostaining kidney biopsy material from patients with a variety of glomerulopathies.
Results:
MCP-1 mRNA was transiently upregulated during the early stages of experimental GN. Message levels increased in association with the monocyte influx and correlated with expression of immunoreactive MCP-1 in the nephritic glomeruli. Glomerular MCP-1 was also found in human inflammatory glomerulopathies, but not in glomerular diseases lacking a prominent monocyte infiltrate.
Conclusions:
These data support a role for MCP-1 in the pathogenesis of glomerular inflammation.
Insights
Monocyte chemoattractant protein-1 (MCP-1) is upregulated in experimental and human glomerulonephritis, supporting its role in recruiting monocytes and driving glomerular inflammation.
Area of Science:
- Nephrology
- Immunology
- Molecular Biology
Background:
- Glomerular monocytes contribute to kidney injury in renal diseases.
- Mediators recruiting monocytes to glomeruli are not well understood.
- Monocyte chemoattractant protein-1 (MCP-1) is a key monocyte chemoattractant produced by mesangial cells.
Purpose of the Study:
- To investigate the in vivo expression of MCP-1 in experimental and human glomerulonephritis (GN).
- To determine the role of MCP-1 in leukocyte recruitment to the glomerulus during GN.
Main Methods:
- Utilized a rodent model of anti-glomerular basement membrane GN to study MCP-1 mRNA and protein.
- Examined MCP-1 presence in human renal biopsy tissue using immunostaining.
Main Results:
- MCP-1 mRNA levels transiently increased in early experimental GN.
- Increased MCP-1 correlated with monocyte influx and protein expression in nephritic glomeruli.
- Glomerular MCP-1 was detected in human inflammatory glomerulopathies with significant monocyte infiltration.
Conclusions:
- The findings support MCP-1's involvement in the pathogenesis of glomerular inflammation.
- MCP-1 plays a significant role in monocyte recruitment during GN.