Osteopontin expression in human cyclosporine toxicity.
BACKGROUND
Osteopontin is a secreted phosphoprotein that has a number of diverse biological functions, including cell signaling, mediation of cell adhesion, migration, and chemoattraction of monocytes/macrophages. Up-regulation of osteopontin expression by proximal tubular epithelium has been demonstrated in both human and rodent models of renal injury in association with macrophage influx.


METHODS
We studied the expression of osteopontin protein and mRNA in renal donor biopsies (N = 7) and renal transplant biopsies with cyclosporine A toxicity (N = 23) by immunohistochemistry and in situ hybridization. Serial tissue sections were immunostained with a monocyte/macrophage marker, CD68, to demonstrate the pattern of macrophage infiltration.


RESULTS
Strong osteopontin expression was observed in the majority of pretransplant donor biopsies in the absence of any macrophage infiltration. In the biopsies with cyclosporine toxicity, osteopontin expression was widespread and demonstrated moderate immunohistochemical signal intensity that did not correlate with the number of interstitial macrophages present.


CONCLUSIONS
Strong osteopontin protein and mRNA expression by tubular epithelium was observed in pretransplant donor biopsies and in biopsies with cyclosporine toxicity without an inflammatory cell infiltration. Therefore, osteopontin expression alone is insufficient to serve as the principal mediator of intrarenal monocyte/macrophage influx in the transplant setting.
Hudkins
K L
KL
Department of Pathology, University of Washington, Seattle, Washington, USA.
Le
Q C
QC
Segerer
S
S
Johnson
R J
RJ
Davis
C L
CL
Giachelli
C M
CM
Alpers
C E
CE
D001707:Biopsy, Needle; D016572:Cyclosporine / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation; D008264:Macrophages / Q000276:immunology; D053495:Osteopontin; D012333:RNA, Messenger / Q000032:analysis; D012795:Sialoglycoproteins / Q000032:analysis / Q000235:genetics*; D014019:Tissue Donors
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin; D016572:Cyclosporine