In situ analysis of C-C chemokine mRNA in human glomerulonephritis

Abstract

Background: Glomerular and tubulointerstitial accumulations of macrophages and T cells are a prominent feature of immune inflammatory glomerulonephritis. The C-C family of chemokines are major mononuclear-cell chemoattractants and may be central to the recruitment of these cells.

Methods: Using in situ hybridization (ISH) we analyzed the expression of mRNA for the C-C chemokines monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha and beta (MIP-1alpha, MIP-1beta) and RANTES in renal biopsy material from twenty patients with glomerulonephritis.

Results: In overt inflammatory glomerulonephritides, chemokine transcripts were differentially expressed by glomerular and tubulointerstitial leukocyte infiltrates, glomerular parietal and proximal tubular epithelial cells and endothelial cells. There was little expression in minimal change nephropathy and normal tissue. Expression of individual chemokines correlated with intrarenal T cell and macrophage infiltrates. Combined immunohistochemistry and ISH demonstrated that 56.9% of cells expressing MCP-1 mRNA were CD68+ve (monocytes/macrophages) and 53% of infiltrating CD68 +ve cells were MCP-1 mRNA positive.

Conclusions: These studies indicate that the in situ production of C-C chemokines by resident and infiltrating cells may play a crucial role in regulating macrophage and T-cell recruitment in glomerulonephritis.