Osteopontin expression in human crescentic glomerulonephritis

Background. Osteopontin is a molecule with diverse biological functions, in cluding cell adhesion, migration, and signaling. The expression of osteopon tin has been demonstrated in a number of models of renal injury in associat ion with accumulations of monocyte/macrophages, including recent reports of osteopontin expression in glomerular crescents in a rat model of anti-glom erular basement membrane glomerulonephritis. Methods. Glomerular expression of osteopontin in biopsies of human crescent ic glomerulonephritis (N = 25), IgA nephropathy with crescents (N = 2), and diffuse proliferative lupus glomerulonephropathy with crescents (N = 1) wa s studied by immunohistochemistry, in situ hybridization, and combined immu nohistochemistry/in situ hybridization. Additionally, antibodies to cell-sp ecific phenotypic markers were used to identify cellular components of the glomerular crescent, which express osteopontin protein and mRNA. Results. All of the crescents present in the biopsies studied contained a s ignificant number of cells that expressed osteopontin protein and mRNA, dem onstrated by immunohistochemistry and in situ hybridization, respectively. Using replicate tissue sections and combined immunohistochemistry/in situ h ybridization, we showed that the majority of the strongly osteopontin-posit ive cells are monocyte/macrophages. In addition to the very strong and cell -associated localization, a weaker and more diffuse pattern of osteopontin protein and mRNA expression could be seen in a number of crescents. None of the osteopontin mRNA-expressing cells could be identified as parietal epit helial cells, CD3-positive T cells, or oc-smooth muscle actin-positive myof ibroblasts. Interstitial monocyte/macrophages did not express osteopontin, except when located in a periglomerular inflammatory infiltrate. Conclusions. Macrophages present in the human glomerular crescent express o steopontin protein and mRNA at a high level. This expression supports a rol e for osteopontin in the formation and progression of the crescentic lesion via chemotactic and signaling properties of the molecule.