Background: Crescent formation is a major feature of rapidly progressive glomerulonephritis and is generally associated with a poor prognosis. Crescents are formed by accumulation of monocyte/macrophages and plasma proteins in Bowman's space, by proliferation of parietal epithelial cells and fibroblasts, and by deposition of the extracellular matrix. Interactions of components of the extracellular matrix with surface receptors of inflammatory cells may be important in crescent formation. One such receptor is the glycoprotein, CD44, whose main ligand is hyaluronate. We performed the present study to determine if hyaluronate is a component of crescents in a model of autoimmune anti-glomerular basement membrane nephritis in rats.
Experimental design: Wistar-Kyoto rats were immunized with bovine glomerular basement membrane, that resulted in severe crescentic glomerulonephritis. Sections of renal tissue were studied with two probes to detect hyaluronate: (a) a soluble CD44-human immunoglobulin fusion protein; and (b) a hyaluronic acid-binding protein. Both probes were revealed by immunofluorescence techniques. The specificity of the reactions was established by selective enzymatic digestions.
Results: Marked accumulation of hyaluronate was demonstrated in developing and sclerosing crescents, in association with local infiltration of T lymphocytes and monocyte/macrophages, cells known to express CD44. Lesser amounts of hyaluronate were found in periglomerular infiltrates.
Conclusions: Hyaluronate is an abundant extracellular component of crescents, and may play a critical role in their formation, by its effects on migration and activation of CD44+ lymphocytes, monocyte/macrophages, fibroblasts and epithelial cells.