IN-SITU ANALYSIS OF C-C CHEMOKINE MESSENGER-RNA IN HUMAN GLOMERULONEPHRITIS

Background. Glomerular and tubulointerstitial accumulations of macroph ages and T cells are a prominent feature of immune inflammatory glomer ulonephritis. 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 (MC P-1), macrophage inflammatory protein-1 alpha and beta (MIP-1 alpha, M IP-1 beta) and RANTES in renal biopsy material from twenty patients wi th glomerulonephritis. Results. In overt inflammatory glomerulonephrit ides, chemokine transcripts were differentially expressed by glomerula r and tubulointerstitial leukocyte infiltrates, glomerular parietal an d proximal tubular epithelial cells and endothelial cells. There was l ittle expression in minimal change nephropathy and normal tissue. Expr ession of individual chemokines correlated with intrarenal T cell and macrophage infiltrates. Combined immunohistochemistry and ISH demonstr ated that 56.9% of cells expressing MCP-1 mRNA were CD68 + ve (monocyt es/macrophages) and 53% of infiltrating CD68 + ve cells were MCP-1 mRN A positive. Conclusions. These studies indicate that the in situ produ ction of C-C chemokines by resident and infiltrating cells may play a crucial role in regulating macrophage and T-cell recruitment in glomer ulonephritis.