Hormones – Cytokines – Signalling
Kidney International (2005) 67, 886–896; doi:10.1111/j.1523-1755.2005.00153.x
Osteopontin expression in acute renal allograft rejection
BASSAM ALCHI, SHINICHI NISHI, DAISUKE KONDO, YOSHIKATSU KANEKO, ASAKO MATSUKI, NAOFUMI IMAI, MITSUHIRO UENO, SEITARO IGUCHI, MINORU SAKATSUME, ICHIEI NARITA, TADASHI YAMAMOTO and FUMITAKE GEJYO
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Blood Purification Center, Niigata University Medical and Dental Hospital, Niigata, Japan; and Department of Structural Pathology, Institute of Nephrology, Niigata University School of Medicine, Niigata, Japan
Correspondence: Bassam Alchi, M.D., Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medicine and Dental Sciences, 1–757 Asahimachi-dori, Niigata 951–8510, Japan. E-mail:bassamalchi@hotmail.com
Received 25 June 2004; Revised 31 August 2004; Accepted 11 October 2004.
Abstract
Osteopontin expression in acute renal allograft rejection.
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.
Conclusion
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.
Keywords:
osteopontin, acute rejection, renal allograft, immunohistochemistry, in situ hybridization, donor, protocol, interstitial inflammation, regeneration, apoptosis
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