MONOCYTE CHEMOTACTIC PEPTIDE-1 EXPRESSION AND MONOCYTE INFILTRATION IN ACUTE RENAL-TRANSPLANT REJECTION

Mononuclear cell infiltration is a common histopathological feature of acute renal transplant rejection, in which it seems to play a key rol e in the pathogenesis of tubulointerstitial lesions. Monocyte chemotac tic peptide-1 (MCP-1) is a specific chemotactic and activating factor for monocytes. Thus, the present study was aimed at evaluating MCP-1 g ene and protein expression in renal biopsies of kidney transplant reci pients with acute deterioration of graft function, and to correlate it with the extent of monocyte infiltration, me studied 20 kidney transp lant recipients with acute graft dysfunction (13 with acute rejection, seven with acute tubular damage). MCP-1 gene and protein expression w ere analyzed by in situ hybridization and immunohistochemistry, respec tively. CD68-positive cells were identified as monocytes. CD68-positiv e cell number and MCP-1 expression were quantified by a computerized i mage analysis system. MCP-1 gene expression, undetectable in normal hu man kidneys, was strikingly increased in patients with acute rejection . The chemokine localized mainly to the proximal tubular cells and to mononuclear-infiltrating cells. In patients with acute tubular damage, the MCP-1 expression, even if higher than in controls, was significan tly lower than in acute rejection. The expression of the chemokine str ictly correlated with the number of infiltrating monocytes (r=0.87, P< 0.05). Moreover, we measured MCP-1 urinary excretion by ELISA, in eigh t normal subjects (36+/-16 pg/mg urine creatinine), in 13 clinically s table transplant recipients (33+/-9 pg/mg, ns vs. normal patients), in 12 transplant recipients with acute rejection (250+/-46 pg/mg, P<0.01 vs. normal patients), and in five transplant recipients with acute tu bular damage (97+/-33 pg/mg, P<0.05 vs. controls and patients with acu te rejection). Urinary MCP-1 excretion directly correlated with renal MCP-1 gene expression (r=0.65, P=0.05). Finally, we observed a signifi cant reduction in MCP-1 urine level in patients with acute rejection, who responded to the antirejection treatment. In conclusion, our data suggest that MCP-1 may play a critical role in modulating monocyte inf lux and consequent tubulointerstitial damage in acute rejection. There fore, an increase in urinary MCP-1 excretion may represent an early si gnal of ongoing acute graft rejection.