Expression of adhesion molecules in allograft renal dysfunction. A distinct diagnostic pattern in rejection and cyclosporine nephrotoxicity.
We have studied in thirty renal biopsies (from 30 cadaver allograft patients) the expression of both LFA-1 and VLA-4 leukocyte adhesion receptors and their respective ICAM-1 and VCAM-1 endothelial cell ligands, during early allograft dysfunction (24 +/- 5 days after transplantation), reversed either by antirejection therapy (n = 14) or by reduction in CsA dose (n = 16). We have found that the levels of expression of the integrin VLA-4 and the activation signal AIM/CD69 (activation inducer molecule) on interstitial cells were significantly (P < 0.001) higher in rejection than in nephrotoxicity. A main differential expression pattern was observed for VCAM-1, the endothelial cell ligand of VLA-4. Interestingly, a strong staining pattern of the renal vascular endothelium and 35% of tubular epithelium was obtained with anti-VCAM-1 antibody in rejection, as compared with a weak reactivity in endothelium and discrete staining pattern on tubules in nephrotoxicity. On the other hand, we found that the mean percentage of infiltrating cells bearing LFA-1 molecules and the intensity of ICAM-1 (a LFA-1 ligand) expression on endothelium were closely similar in both rejection and CsA nephrotoxicity. Nevertheless, a discrete significant (P < 0.05) "de novo" expression of ICAM-1 was present on tubular cells during rejection. Our results strongly suggest that in rejection the interstitial cell infiltrate seems to be facilitated by the contribution of both LFA-1/ICAM-1 and VLA-4/VCAM-1 cell adhesion mechanisms, and also that VLA-4/VCAM-1 leukocyte interaction does not play a role in cases with CsA nephrotoxicity. Furthermore, the differential expression patterns of VLA-4 and VCAM-1 molecules found between rejection and CsA nephrotoxicity could provide valuable immunohistochemical criteria in the diagnosis of allograft dysfunction.
Mampaso
F
F
Department of Pathology, Hospital Ramon y Cajal, Madrid, Spain.
Sanchez-Madrid
F
F
Marcen
R
R
Molina
A
A
Pascual
J
J
Bricio
T
T
Martin
A
A
Alvarez
V
V
D000328:Adult; D002102:Cadaver; D015815:Cell Adhesion Molecules / Q000502:physiology*; D016572:Cyclosporine / Q000633:toxicity; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000737:chemistry; D007674:Kidney Diseases / Q000139:chemically induced / Q000175:diagnosis* / Q000378:metabolism; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D007962:Leukocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous / Q000276:immunology
D015815:Cell Adhesion Molecules; D016572:Cyclosporine