title: Osteopontin expression in human crescentic glomerulonephritis.
abstract: Osteopontin expression in human crescentic glomerulonephritis.
  
  
  BACKGROUND
  Osteopontin is a molecule with diverse biological functions, including cell adhesion, migration, and signaling. The expression of osteopontin has been demonstrated in a number of models of renal injury in association with accumulations of monocyte/macrophages, including recent reports of osteopontin expression in glomerular crescents in a rat model of anti-glomerular basement membrane glomerulonephritis.
  
  
  METHODS
  Glomerular expression of osteopontin in biopsies of human crescentic glomerulonephritis (N = 25), IgA nephropathy with crescents (N = 2), and diffuse proliferative lupus glomerulonephropathy with crescents (N = 1) was studied by immunohistochemistry, in situ hybridization, and combined immunohistochemistry/in situ hybridization. Additionally, antibodies to cell-specific 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 significant number of cells that expressed osteopontin protein and mRNA, demonstrated by immunohistochemistry and in situ hybridization, respectively. Using replicate tissue sections and combined immunohistochemistry/in situ hybridization, we showed that the majority of the strongly osteopontin-positive 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 epithelial cells, CD3-positive T cells, or alpha-smooth muscle actin-positive myofibroblasts. Interstitial monocyte/macrophages did not express osteopontin, except when located in a periglomerular inflammatory infiltrate.
  
  
  CONCLUSIONS
  Macrophages present in the human glomerular crescent express osteopontin protein and mRNA at a high level. This expression supports a role for osteopontin in the formation and progression of the crescentic lesion via chemotactic and signaling properties of the molecule.
authors.affiliation: Department of Pathology and Division of Nephrology, University of Washington, Seattle, Washington 98195, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Hudkins
authors.forename: C M
authors.initials: CM
authors.lastname: Giachelli
authors.forename: F
authors.initials: F
authors.lastname: Eitner
authors.forename: W G
authors.initials: WG
authors.lastname: Couser
authors.forename: R J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: C E
authors.initials: CE
authors.lastname: Alpers
mesh_terms: D005921:Glomerulonephritis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053495:Osteopontin; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin