Expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in human crescentic glomerulonephritis.

Abstract

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. 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. 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.