MONOCYTE CHEMOTACTIC PEPTIDE-1 EXPRESSION IN ACUTE AND CHRONIC HUMAN NEPHRITIDES - A PATHOGENETIC ROLE IN INTERSTITIAL MONOCYTES RECRUITMENT

Tubulointerstitial damage is a common histopathological feature of acu te and chronic renal diseases and a prognostic indicator of renal func tion outcome, Monocytes infiltrating the interstitium, through the rel ease of cytokines and/or growth factors, may play a key role in the pa thogenesis of tubulointerstitial damage. Monocyte chemotactic peptide- 1 (MCP-1) is a specific and powerful chemoattractant and activating fa ctor for monocytes, This study investigated MCP-1 expression and its c orrelation with monocyte infiltration and tubulointerstitial damage in biopsies of patients with acute interstitial nephritis (AIN) and a ch ronic glomerulonephritis, namely immunoglobulin A nephropathy (IgAN), often characterized by tubulointerstitial involvement. Six patients wi th AIN and 20 patients with IgAN, nine with mild (G1 to 2) and 11 with moderate to severe histologic lesions (G3 to 5), were studied. MCP-1 gene and protein expression were evaluated by in situ hybridization an d immunohistochemistry. Infiltrating CD68-positive cells were identifi ed as monocytes. MCP-1, weakly expressed in normal kidneys, was clearl y upregulated in AIN biopsies. The gene and the protein expression wer e primarily localized in tubular and glomerular parietal epithelial ce lls, as well as in infiltrating mononuclear cells. In IgAN, a striking increase in MCP-1 mRNA and protein expression was observed only in th e biopsies with moderate to severe lesions, with a pattern of expressi on similar to AIN. The MCP-1 expression strictly correlated with monoc yte infiltrates and tubulointerstitial damage, In addition, the urinar y excretion of this chemokine was studied in 17 IgAN patients. MCP-1 p rotein concentration was higher, compared with healthy subjects, in Ig AN patients, especially in the G3 to 5 group, and directly correlated with the renal MCP-1 gene expression. In conclusion, these data sugges t that production of MCP-1 in the tubulointerstitial compartment may p lay a key role in modulating monocytes influx and, consequently, tubul ointerstitial damage.