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Updated: Aug 17, 2026
Isolation of Glomeruli and In Vivo Labeling of Glomerular Cell Surface Proteins
Published on: January 18, 2019
MIP-1alpha and MCP-1 contribute to crescents and interstitial lesions in human crescentic glomerulonephritis
T Wada1, K Furuichi, C Segawa-Takaeda
1First Department of Internal Medicine, School of Medicine, Kanazawa University, Japan. twada@med.kanazawa-u.ac.jp
Background:
The precise molecular mechanisms of macrophage (Mphi) recruitment and activation in crescentic glomerulonephritis remain to be investigated. We hypothesized that locally produced macrophage inflammatory protein (MIP)-1alpha and monocyte chemoattractant protein (MCP)-1 via the chemokine receptors participate in the pathophysiology of human crescentic glomerulonephritis by recruiting and activating Mphi.
Methods:
We investigated the levels of MIP-1alpha and MCP-1 by enzyme-linked immunosorbent assay (ELISA) in 20 healthy subjects, 20 patients with crescentic glomerulonephritis, and 41 control patients with various other renal diseases. The presence of MIP-1alpha, MCP-1, and the cognate chemokine receptor for MIP-1alpha, CCR5, in the diseased kidneys was evaluated by immunohistochemical and in situ hybridization analyses.
Results:
MIP-1alpha-positive cells were mainly detected in crescentic lesions, whereas MCP-1 was mainly in the interstitium. In addition, we detected CCR5-positive cells in diseased glomeruli and interstitium. Urinary MIP-1alpha was detected in crescentic glomerulonephritis, even though it was below detectable levels in healthy subjects and in patients with other renal diseases without crescents. Urinary MIP-1alpha levels in the patients with crescentic glomerulonephritis were well correlated with the percentage of cellular crescents and the number of CD68-positive infiltrating cells and CCR5-positive cells in the glomeruli. However, urinary MCP-1 levels were well correlated with the percentage of both total crescents and fibrocellular/fibrous crescents and the number of CD68-positive infiltrating cells in the interstitium. Moreover, elevated urinary levels of both MIP-1alpha and MCP-1 dramatically decreased during glucocorticoid therapy-induced convalescence.
Conclusions:
These observations suggest that locally produced MIP-1alpha may be involved in the development of cellular crescents in the acute phase via CCR5 and that MCP-1 may be involved mainly in the development of interstitial lesions in the chronic phase when fibrocellular/fibrous crescents are present, possibly through Mphi recruitment and activation.
Insights
Macrophage inflammatory protein (MIP)-1alpha and monocyte chemoattractant protein (MCP)-1 play key roles in crescentic glomerulonephritis. MIP-1alpha is linked to acute cellular crescent development, while MCP-1 is associated with chronic interstitial lesions.
Area of Science:
- Nephrology
- Immunology
- Pathophysiology
Background:
- The molecular mechanisms of macrophage recruitment and activation in crescentic glomerulonephritis are not fully understood.
- Macrophage inflammatory protein (MIP)-1alpha and monocyte chemoattractant protein (MCP)-1 are hypothesized to be involved in crescentic glomerulonephritis pathogenesis.
- These chemokines may recruit and activate macrophages via chemokine receptors.
Purpose of the Study:
- To investigate the roles of MIP-1alpha and MCP-1 in human crescentic glomerulonephritis.
- To determine the correlation between chemokine levels and kidney lesions.
- To evaluate the effect of therapy on chemokine levels.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to measure MIP-1alpha and MCP-1 levels in healthy subjects and patients.
- Immunohistochemical and in situ hybridization analyses were performed to detect chemokines and receptors in kidney tissue.
- Urinary chemokine levels were correlated with clinical and histological findings.
Main Results:
- MIP-1alpha was primarily found in crescentic lesions, while MCP-1 was mainly in the interstitium.
- Urinary MIP-1alpha levels correlated with cellular crescents and infiltrating cells in glomeruli.
- Urinary MCP-1 levels correlated with interstitial lesions and infiltrating cells in the interstitium.
- Elevated urinary MIP-1alpha and MCP-1 levels decreased significantly with glucocorticoid therapy.
Conclusions:
- Locally produced MIP-1alpha may contribute to acute cellular crescent formation via CCR5.
- MCP-1 may be involved in chronic interstitial lesion development, possibly through macrophage recruitment and activation.
- Both MIP-1alpha and MCP-1 levels decrease with successful therapy, indicating their role in active disease.
