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Expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in human crescentic
1Department of Pathology, Seoul National University College of Medicine, Chongno-gu, Seoul, South Korea.
Insights
Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are upregulated in crescentic glomerulonephritis. ICAM-1 is involved in early leukocyte recruitment, while parietal epithelial cells express both molecules in cellular crescents.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Glomerulonephritis involves crescent formation, where intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) may play crucial roles.
- Understanding the expression and cellular origin of these adhesion molecules is vital for elucidating disease mechanisms.
Purpose of the Study:
- To evaluate the expression patterns of ICAM-1 and VCAM-1 in human crescentic glomerulonephritis.
- To determine the cellular origin of ICAM-1 and VCAM-1 within crescentic lesions.
Main Methods:
- Immunohistochemistry was used to examine ICAM-1 and VCAM-1 protein expression in renal biopsies of crescentic glomerulonephritis and controls.
- RNA in-situ hybridization was employed to assess mRNA expression, with double-labeling performed using cytokeratin and CD68 markers.
Main Results:
- ICAM-1 and VCAM-1 proteins were over-expressed in cellular crescents, with ICAM-1 levels decreasing in fibrous crescents.
- VCAM-1 was expressed in fibrous crescents by epithelial cells, while ICAM-1 expression was significantly higher in glomerular tufts of cellular/fibrocellular crescents compared to VCAM-1.
- mRNA expression paralleled protein levels, with signals mainly localized to cytokeratin-positive, CD68-negative cells in crescentic lesions.
Conclusions:
- Glomerular parietal epithelial cells up-regulate both ICAM-1 and VCAM-1 in cellular crescents.
- Persistent VCAM-1, but not ICAM-1, over-expression occurs in epithelial cells within fibrous crescents.
- ICAM-1 appears to be involved in the early recruitment of leukocytes into glomeruli during crescentic glomerulonephritis.
Aims:
In glomerulonephritis, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) may play important roles in the formation of crescents. These studies are designed to evaluate the expression patterns of ICAM-1 and VCAM-1 in human crescentic glomerulonephritis and to determine the cellular origin of adhesion molecules in the crescentic lesions.
Methods And Results:
We examined the expression of ICAM-1 and VCAM-1 proteins in renal biopsies with cellular (n=7), fibrocellular (n=9) or fibrous (n=4) crescentic glomerulonephritis, and six controls by immunohistochemistry. mRNA expression of ICAM-1 and VCAM-1 was further evaluated by RNA in-situ hybridization. Cytokeratin or CD68 immunohistochemistry was performed on the same sections, where in-situ hybridization had been carried out. In cellular crescents, ICAM-1 and VCAM-1 proteins were over-expressed to a similar extent. Of the three types of crescents, the extent of ICAM-1 immunopositivity was the greatest in the cellular crescents and decreased towards the fibrous crescents (P < 0.05). Yet the extent of VCAM-1 immunoreactivity was not different between the types. Fibrous crescents still contained some epithelial cells and showed only VCAM-1 expression. In the glomeruli with cellular or fibrocellular crescents, the extent of ICAM-1 immunopositivity in the glomerular tufts was significantly larger than that of VCAM-1 (P < 0.05). In an in-situ hybridization study, the mRNA expression patterns of ICAM-1 and VCAM-1 paralleled their protein expressions. A double-labelling study showed that the signal for ICAM-1 and VCAM-1 mRNAs was mainly present in cytokeratin-positive and CD68-negative cells in the crescentic lesions.
Conclusions:
These results suggest that glomerular parietal epithelial cells in cellular crescents up-regulate both ICAM-1 and VCAM-1, and that some epithelial cells retained in fibrous crescents persistently over-express VCAM-1, but not ICAM-1. They also suggest that ICAM-1 is involved in early leucocyte recruitment into glomeruli in crescentic glomerulonephritis.