Potential role for monocyte chemotactic protein-4 (MCP-4) in monocyte/macrophage recruitment in acute renal inflammation

The CC chemokine, monocyte chemoattractant protein-4 (MCP-4), is an importa nt chemoattractant for monocytes and T cells. Recent data indicate a role i n renal inflammation. This study has used in situ hybridization and immunoh istochemical analysis of cryostat sections of biopsy material taken from pa tients with acute renal allograft rejection and vasculitic glomerulonephrit is to demonstrate renal expression of MCP-4, both at message and protein le vel. MCP-4 was primarily expressed at peritubular, periglomerular, and peri vascular sites, irrespective of the inflammatory condition, and was associa ted with infiltrating CD3-positive lymphocytes and CD68-positive monocyte/m acrophages. In addition, proximal tubular epithelial cells grown in culture from cortical fragments of human kidney showed low levels of constitutive MCP-4 expression, detectable by western blotting; this expression of MCP-4 was up-regulated in response to the pro-inflammatory cytokines, tumour necr osis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), CCR3-, CCR5 - and CCR2-expressing leukocyte populations were identified at sites of MCP -4 expression. Double-staining techniques revealed that CC chemokine recept or-expressing cells were primarily CD68-positive. These studies suggest an important role for MCP-4 in the recruitment and retention of monocytes/macr ophages in renal inflammation. Copyright (C) 2001 John Wiley & Sons, Ltd.