title: Osteopontin expression in acute renal allograft rejection.
abstract: BACKGROUND
  Osteopontin (OPN) is a potent chemoattractant for mononuclear cells that is up-regulated in various inflammatory states of the kidney. The role of OPN and its expression in human renal allograft rejection are unknown.
  
  
  METHODS
  We examined by immunohistochemistry and in situ hybridization, renal biopsies from patients with acute rejection (N= 22), protocol biopsies without rejection (N= 9), and perioperative donor biopsies (N= 35) for intrarenal expression of OPN, and its correlation with clinical, laboratory, and histopathologic parameters. In the rejection biopsies, interstitial monocyte/macrophage infiltration, tubulointerstitial cell proliferation/regeneration and apoptosis were investigated.
  
  
  RESULTS
  In the majority of rejection biopsies, OPN expression by proximal tubular epithelium was widespread, and tended to be enhanced in the tubules surrounded by numerous inflammatory cells. Conversely, in patients that did not experience episodes of rejection and in donor biopsies, OPN expression by proximal tubules was nil or weak. OPN mRNA was colocalized with its translated protein in the renal tubular epithelium. OPN expression positively correlated with the degree of interstitial inflammation (P < 0.05), CD68+ monocyte infiltration (P < 0.01), Ki-67+ regenerating tubular and interstitial cells (P < 0.05 and P < 0.005, respectively), but not with terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL)-positive apoptotic tubular cells.
  
  
  CONCLUSIONS
  These data suggest that inducible expression of OPN in the tubular epithelium may have a pathogenic role in acute renal allograft rejection by mediating interstitial monocyte infiltration and possibly tubular regeneration.
authors.affiliation: Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. bassamalchi@hotmail.com
authors.forename: Bassam
authors.initials: B
authors.lastname: Alchi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nishi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kondo
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Asako
authors.initials: A
authors.lastname: Matsuki
authors.forename: Naofumi
authors.initials: N
authors.lastname: Imai
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ueno
authors.forename: Seitaro
authors.initials: S
authors.lastname: Iguchi
authors.forename: Minoru
authors.initials: M
authors.lastname: Sakatsume
authors.forename: Ichiei
authors.initials: I
authors.lastname: Narita
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Fumitake
authors.initials: F
authors.lastname: Gejyo
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D017209:Apoptosis; D005260:Female; D006084:Graft Rejection / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation; D008264:Macrophages / Q000502:physiology; D008297:Male; D008875:Middle Aged; D053495:Osteopontin; D012333:RNA, Messenger / Q000032:analysis; D012795:Sialoglycoproteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014184:Transplantation, Homologous
chemical_list: D019394:Ki-67 Antigen; D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin